Doxycycline

Last updated

Doxycycline
Doxycycline structure.svg
Doxycycline ball-and-stick model from xtal 2012.png
Clinical data
Pronunciation /ˌdɒksɪˈsaɪkliːn/
DOKS-ih-SYE-kleen
Trade names Vibramycin, others
AHFS/Drugs.com Monograph
MedlinePlus a682063
License data
Pregnancy
category
  • AU:D
Routes of
administration 		By mouth, intravenous [1]
ATC code
Legal status
Legal status
  • AU: S4 (Prescription only)
  • UK: POM (Prescription only)
  • US: ℞-only
Pharmacokinetic data
Bioavailability ~100%
Protein binding 80–90%
Metabolism Negligible
Elimination half-life 10–22 hours
Excretion Mainly feces, 40% urine
Identifiers
  • (4S,4aR,5S,5aR,6R,12aS)-4-(Dimethylamino)-3,5,10,12,12a-pentahydroxy-6-methyl-1,11-dioxo-1,4,4a,5,5a,6,11,12a-octahydrotetracene-2-carboxamide
CAS Number
PubChem CID
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard 100.008.429 OOjs UI icon edit-ltr-progressive.svg
Chemical and physical data
Formula C22H24N2O8
Molar mass 444.440 g·mol−1
3D model (JSmol)
  • CN(C)[C@@H]3C(\O)=C(\C(N)=O)C(=O)[C@@]4(O)C(/O)=C2/C(=O)c1c(cccc1O)[C@H](C)[C@H]2[C@H](O)[C@@H]34
  • InChI=1S/C22H24N2O8.H2O/c1-7-8-5-4-6-9(25)11(8)16(26)12-10(7)17(27)14-15(24(2)3)18(28)13(21(23)31)20(30)22(14,32)19(12)29;/h4-7,10,14-15,17,25,27-29,32H,1-3H3,(H2,23,31);1H2/t7-,10+,14+,15-,17-,22-;/m0./s1
  • Key:XQTWDDCIUJNLTR-CVHRZJFOSA-N

Doxycycline is a broad-spectrum antibiotic of the tetracycline class used in the treatment of infections caused by bacteria and certain parasites. [1] It is used to treat bacterial pneumonia, acne, chlamydia infections, Lyme disease, cholera, typhus, and syphilis, [1] and is sometimes used to prevent malaria. [2] [3] Doxycycline may be taken by mouth or intravenously. [1]

Contents

Common side effects include diarrhea, nausea, vomiting, abdominal pain, and an increased risk of sunburn. [1] Use during pregnancy is not recommended. [1] Doxycycline can be used in children of all ages, including for Lyme disease and rickettsial infections. [4] [5] Like other agents of the tetracycline class, it slows or kills bacteria by inhibiting protein production. [1] [6] It kills Plasmodium —microorganisms associated with malaria—by targeting a plastid organelle, the apicoplast. [7] [8]

Doxycycline post-exposure prophylaxis (doxyPEP) is also used to prevent sexually transmitted infections, particularly in men who have sex with men, and is supported by CDC guidelines. [9] [10]

Doxycycline hyclate Doxycycline hyclate substance photo2.jpg
Doxycycline hyclate

Doxycycline was patented in 1957 and came into commercial use in 1967. [11] [12] It is on the World Health Organization's List of Essential Medicines. [13] Doxycycline is available as a generic medicine. [1] [14] In 2023, it was the 77th most commonly prescribed medication in the United States, with more than 8 million prescriptions. [15] [16]

Medical uses

Generic 100 mg doxycycline capsules Doxycycline 100mg capsules.jpg
Generic 100 mg doxycycline capsules
A package of generic doxycycline Doksiciklin 100 091208.jpg
A package of generic doxycycline

Like all tetracycline antibiotics, doxycycline is indicated for susceptible Gram-positive and Gram-negative bacterial infections, including respiratory tract infections and urinary tract infections. Beyond these general tetracycline indications, doxycycline is frequently used to treat Lyme disease, chronic prostatitis, sinusitis, pelvic inflammatory disease, [17] [18] severe acne, rosacea, [19] [20] [21] and rickettsial infections. [22] The efficiency of oral doxycycline for treating papulopustular rosacea and adult acne is not solely based on its antibiotic properties, but also on its anti-inflammatory and anti-angiogenic properties. [23]


Antibacterial

General indications

Doxycycline is a broad-spectrum antibiotic that is employed in the treatment of numerous bacterial infections. It is effective against bacteria such as Moraxella catarrhalis (a cause of respiratory tract infections), Brucella melitensis (a cause of brucellosis), Chlamydia pneumoniae (a cause of atypical pneumonia), and Mycoplasma pneumoniae (a cause of pneumonia). Additionally, doxycycline is used in the prevention and treatment of serious conditions like anthrax, leptospirosis, bubonic plague, and Lyme disease. However, some bacteria have developed resistance to doxycycline, including Haemophilus species, Mycoplasma hominis , and Pseudomonas aeruginosa . [24] [25]

Specifically, doxycycline is indicated for treatment of the following diseases: [26] [27]

Indications for Gram-negative bacteria

When bacteriologic susceptibility testing (laboratory tests confirming the bacteria are sensitive to the drug) indicates appropriate susceptibility, doxycycline may be used to treat these infections caused by Gram-negative bacteria: [26] [27]

Indications for Gram-positive bacteria

Some Gram-positive bacteria have developed resistance to doxycycline. Tetracycline resistance rates vary by geographic region; for example, resistance in Streptococcus pyogenes ranges from about 1% in Sweden to over 80% in China, and a pooled global resistance rate of approximately 67% has been reported for Enterococcus faecalis . [26] [27] When bacteriologic susceptibility testing indicates appropriate susceptibility to the drug, doxycycline may be used to treat these infections caused by Gram-positive bacteria: [26] [27]

Penicillin contraindication

When penicillin is contraindicated, doxycycline can be used to treat: [26] [27]

Use as adjunctive therapy

Doxycycline is used as an adjunctive therapy for severe acne, [37] [26] [27] acute intestinal amebiasis, [38] and chancroid. [38]

Subantimicrobial-dose doxycycline (SDD) is widely used as an adjunctive treatment to scaling and root planing for periodontitis. [39] SDD is also used to treat skin conditions such as acne and rosacea, [19] [40] [41] including ocular rosacea. In ocular rosacea, treatment period is 2 to 3 months. After discontinuation of doxycycline, recurrences may occur within three months; therefore, many studies recommend either slow tapering or treatment with a lower dose over a longer period of time. [42]

As prophylaxis against sexually transmitted infections

Doxycycline is used as post-exposure prophylaxis (PEP) to prevent certain sexually transmitted infections, known as doxycycline post-exposure prophylaxis (doxyPEP). A landmark randomized trial in San Francisco found that a single 200 mg dose of doxycycline taken within 72 hours after condomless sex reduced the overall incidence of bacterial STIs by approximately two-thirds among men who have sex with men (MSM) and transgender women, with reductions of 87-88% for chlamydia, 73-87% for syphilis, and 55% for gonorrhea. [10] However, a separate trial found doxyPEP was not effective in cisgender women. [43]

In June 2024, the US Centers for Disease Control and Prevention (CDC) issued clinical guidelines recommending doxyPEP for MSM and transgender women with at least one bacterial STI in the prior 12 months. [9] The Australasian Society for HIV Medicine issued a more cautious consensus statement recommending doxyPEP only for syphilis prevention in MSM, citing concerns that the risk of increasing antimicrobial resistance, especially in Neisseria gonorrhoeae , outweighed the benefits for other STIs. [44] Use of doxyPEP has been associated with tetracycline resistance in N. gonorrhoeae. [45]

Use in combination

The first-line treatment for brucellosis is a combination of doxycycline and streptomycin. The second-line treatment is a combination of doxycycline and rifampicin (rifampin). [46]

Antimalarial

Doxycycline is active against the erythrocytic stages of Plasmodium falciparum , a protozoan parasite that causes malaria, but it is not active against the gametocytes of P. falciparum. [47] As such, doxycycline is used to prevent malaria, [48] but not recommended alone for initial treatment of malaria, even when the parasite is doxycycline-sensitive, because the antimalarial effect of doxycycline is delayed by 48 to 96 hours owing to a "delayed death" mechanism in which parasites complete their current replication cycle before dying in the next cycle. For this reason, doxycycline prophylaxis must be continued for four weeks after leaving a malarious area, compared with only seven days for atovaquone/proguanil. [49]

Doxycycline blocks protein production in the apicoplast (an organelle) of P. falciparum. This disrupts the parasite's ability to produce fatty acids, which are essential for its growth, and impairs the production of heme, a cofactor. These effects occur late in the parasite's life cycle during the blood stage (the erythrocytic cycle, when the parasite replicates inside human red blood cells). [50] By blocking important processes in the parasite, doxycycline both inhibits the growth and prevents the replication of P. falciparum. It does not directly kill living P. falciparum, but creates conditions that prevent their growth and replication. [51]

The World Health Organization (WHO) guidelines state that the combination of doxycycline with either artesunate or quinine may be used for the treatment of uncomplicated malaria due to P. falciparum or following intravenous treatment of severe malaria. [52]

Deworming

Doxycycline can be used against parasitic nematodes (worms) that cause filariasis. It kills symbiotic bacteria of the genus Wolbachia in the reproductive tracts of the nematodes, making the nematodes sterile (unable to reproduce). [53] This reduces transmission of diseases such as onchocerciasis and elephantiasis. [54] A randomized controlled trial showed that an eight-week course of doxycycline almost eliminates the release of microfilariae (larval offspring of the nematodes). [55]

Spectrum of susceptibility

Doxycycline has been used successfully to treat sexually transmitted, respiratory, and eye infections. Representative pathogenic genera include Chlamydia, Streptococcus, Ureaplasma, Mycoplasma , and others. The minimum inhibitory concentration for a few medically significant microorganisms are: [56]

Sclerotherapy

Doxycycline is also used for sclerotherapy in venous and lymphatic malformations, as well as post-operative lymphoceles (collections of lymph fluid outside of lymphatic vessels). [57]

Off-label use

Doxycycline is used off-label in the treatment of transthyretin amyloidosis (ATTR). In combination with tauroursodeoxycholic acid, doxycycline has been shown to disrupt transthyretin (TTR) fibrils in existing amyloid deposits of ATTR patients, and is being investigated as a potential treatment option for this condition. [58]

Routes of administration

Doxycycline can be administered orally or intravenously. [1]

The combination of doxycycline with dairy, antacids, calcium supplements, iron products, laxatives containing magnesium, or bile acid sequestrants may decrease absorption of doxycycline, though these interactions are not inherently dangerous. [59] [60]

Doxycycline has a high oral bioavailability, as it is almost completely absorbed in the stomach and proximal small intestine. [19] Unlike older tetracyclines, whose absorption is substantially reduced by food, doxycycline absorption is only modestly affected: co-administration of dairy products reduces the serum concentration of doxycycline by about 20%, compared with a 50% reduction for tetracycline. [19] Doxycycline absorption is inhibited by cations with a 2+ or 3+ charge (divalent and trivalent cations), such as iron, bismuth, aluminum, calcium, and magnesium. [19] Doxycycline forms unstable complexes with these metal ions in the acidic environment of the stomach; most of these complexes dissociate in the small intestine, allowing the drug to be absorbed. However, some doxycycline remains complexed with metal ions in the duodenum, resulting in a slight decrease in absorption. [19]

Contraindications

Doxycycline is contraindicated (should not be used) in patients with severe liver disease or those taking isotretinoin or other retinoids, as both tetracyclines and retinoids can cause intracranial hypertension (increased pressure around the brain) in rare cases. [59]

Pregnancy and lactation

Doxycycline is categorized by the FDA as a class D drug in pregnancy, meaning there is evidence of risk to the fetus but the benefits may outweigh the risks in certain situations. Doxycycline crosses into breast milk and is therefore a concern during breastfeeding. [61] Other tetracycline antibiotics are contraindicated in pregnancy and up to eight years of age, due to the potential for disrupting bone and tooth development. [62] The FDA includes a class warning for all tetracyclines about staining of teeth (typically yellow to brown discoloration) and decreased development of dental enamel in children exposed to tetracyclines in utero , during breastfeeding, or during early childhood (under eight years of age). [63] However, the FDA has acknowledged that the actual risk of dental staining of primary teeth is undetermined for doxycycline specifically. The best available evidence indicates that doxycycline has little or no effect on hypoplasia (underdevelopment) of dental enamel or on staining of primary teeth (baby teeth). The US Centers for Disease Control and Prevention (CDC) recommends the use of doxycycline for treatment of Q fever and tick-borne rickettsial diseases in children of all ages, and some researchers advocate for its use in children with malaria as well. [64]

Adverse effects

Adverse effects of doxycycline are similar to those of other members of the tetracycline antibiotic group. Doxycycline can cause gastrointestinal upset. [65] [66] Oral doxycycline can cause pill esophagitis, particularly when it is swallowed without adequate fluid, or by persons with difficulty swallowing or reduced gastrointestinal motility. [67] Doxycycline is less likely than other antibiotic drugs to cause Clostridioides difficile colitis . [68]

An erythematous (red) rash in sun-exposed parts of the body has been reported to occur in 7.3-21.2% of persons taking doxycycline as prophylaxis against malaria. The rash resolves upon discontinuation of the drug. One study examined the tolerability of various malaria prophylactic regimens and found doxycycline did not cause a significantly higher percentage of skin events (such as rash, itching, or photosensitivity) when compared with other antimalarials. [69]

Unlike some other members of the tetracycline group, doxycycline may be used in those with renal impairment, because it is primarily excreted via the feces rather than the kidneys, and does not accumulate to toxic levels when kidney function is reduced. [70]

Doxycycline use has been associated with increased risk of inflammatory bowel disease. [71] In one large retrospective study, patients who were prescribed doxycycline for their acne had a 2.25-fold greater risk of developing Crohn's disease. [72]

Interactions

Previously, doxycycline was believed to impair the effectiveness of many types of hormonal contraception due to induction of CYP450 enzymes (a family of liver enzymes that break down drugs, potentially accelerating the metabolism of hormonal contraceptives). Research has shown no significant loss of effectiveness in oral contraceptives while using most tetracycline antibiotics (including doxycycline), although many physicians still recommend the use of barrier contraception for people taking the drug to prevent unwanted pregnancy. [73] [74] [70]

Pharmacology

Pharmacodynamics

Doxycycline, like other tetracycline antibiotics, is bacteriostatic. It works by preventing bacteria from reproducing by inhibiting protein synthesis. [75]

Doxycycline is highly lipophilic, so it can easily enter cells, meaning the drug is readily absorbed and has a large volume of distribution (it distributes widely throughout body tissues rather than remaining in the blood). It can also be re-absorbed in the renal tubules and gastrointestinal tract due to its high lipophilicity, giving it a long elimination half-life. In patients with kidney failure, doxycycline does not accumulate to toxic levels because the body compensates by increasing excretion through the feces. [66] [76] Doxycycline-metal ion complexes are unstable in acidic conditions, therefore more doxycycline enters the duodenum for absorption than older tetracycline compounds such as tetracycline and oxytetracycline. In addition, food has less effect on the absorption of doxycycline than on other tetracyclines, with doxycycline serum concentrations being reduced by about 20% by test meals compared with 50% for tetracycline. [77]

Mechanism of action

Doxycycline is a broad-spectrum bacteriostatic antibiotic. It inhibits the synthesis of bacterial proteins by binding to the 30S ribosomal subunit, which is only found in bacteria. [65] [76] This prevents the binding of transfer RNA to messenger RNA at the ribosomal subunit, meaning amino acids cannot be added to polypeptide chains and new proteins cannot be made. This stops bacterial growth, giving the immune system time to kill the bacteria. [78]

In rosacea treatment, doxycycline inhibits neutrophil chemotaxis and oxidative bursts (common mechanisms of inflammation and reactive oxygen species activity in rosacea), and it also suppresses matrix metalloproteases and kallikrein 5 which in turn reduce the expression of the human cathelicidin antimicrobial peptide (LL-37) and limit downstream inflammatory cascades. [23]

Absorption and excretion

Doxycycline is almost completely absorbed from the stomach and upper part of the small intestine (duodenum and jejunum). It reaches highest concentrations in the blood plasma after one to two hours and has a high plasma protein binding rate of about 80–90%. Doxycycline penetrates into almost all tissues and body fluids. Very high concentrations are found in the gallbladder, liver, kidneys, lungs, breast milk, bones, and genitals; low concentrations are found in saliva, aqueous humor, cerebrospinal fluid (CSF), and especially in inflamed meninges. [59] [79] [80] By comparison, the tetracycline antibiotic minocycline penetrates significantly better into the CSF and meninges. [81]

Doxycycline metabolism (breakdown by the body) is negligible. It is actively excreted into the gut (in part via the gallbladder, in part directly from blood vessels), where some of it is inactivated by forming chelates. About 40% are eliminated via the kidneys, much less in people with end-stage kidney disease. The biological half-life is 18 to 22 hours (16 ± 6 hours according to another source [79] ) in healthy people, slightly longer in those with end-stage kidney disease, and significantly longer in those with liver disease. [59] [79] [80]

Chemistry

Expired tetracyclines or tetracyclines allowed to stand at a pH less than 2 are reported to be nephrotoxic due to the formation of a degradation product, anhydro-4-epitetracycline [82] [83] causing Fanconi syndrome. [84] In the case of doxycycline, the absence of a hydroxyl group in C-6 prevents the formation of the nephrotoxic compound. [83] Nevertheless, tetracyclines and doxycycline itself have to be taken with caution in patients with kidney injury, as they can worsen azotemia due to catabolic effects. [84]

Chemical properties

Doxycycline, doxycycline monohydrate and doxycycline hyclate are yellow, crystalline powders with a bitter taste. The latter smells faintly of ethanol, a 1% aqueous solution has a pH of 2–3, and the specific rotation is  −110° cm3/dm·g in 0.01  N methanolic hydrochloric acid. [79]

Solubility [79]
Solubility inDoxycyclineDoxycycline monohydrateDoxycycline hyclate
Watervery slightlyvery slightlyfreely
Ethanolvery slightlyvery slightlysparingly
Aqueous acidsfreelyfreely
Alkali hydroxyde solutionsfreelyfreely
Chloroform very slightlypractically insolublepractically insoluble
Diethyl ether insolublepractically insolublepractically insoluble

History

After penicillin revolutionized the treatment of bacterial infections in World War II, many chemical companies moved into the field of discovering antibiotics by bioprospecting. American Cyanamid was one of these, and in the late 1940s chemists there discovered chlortetracycline, the first member of the tetracycline class of antibiotics. [6] Shortly thereafter, scientists at Pfizer discovered oxytetracycline and it was brought to market. Both compounds, like penicillin, were natural products and it was commonly believed that nature had perfected them, and further chemical changes could only degrade their effectiveness. Scientists at Pfizer led by Lloyd Conover modified these compounds, which led to the invention of tetracycline itself, the first semi-synthetic antibiotic. Charlie Stephens' group at Pfizer worked on further analogs and created one with greatly improved stability and pharmacological efficacy: doxycycline. It was clinically developed in the early 1960s and approved by the US Food and Drug Administration (FDA) in 1967. [6]

As its patent grew near to expiring in the early 1970s, the patent became the subject of lawsuit between Pfizer and International Rectifier [85] that was not resolved until 1983; at the time it was the largest litigated patent case in US history. [86] Instead of a cash payment for infringement, Pfizer took the veterinary and feed-additive businesses of International Rectifier's subsidiary, Rachelle Laboratories. [86]

In January 2013, the FDA reported shortages of some, but not all, forms of doxycycline "caused by increased demand and manufacturing issues". [87] Companies involved included an unnamed major generics manufacturer that ceased production in February 2013, Teva (which ceased production in May 2013), Mylan, Actavis, and Hikma Pharmaceuticals. [88] [89] The shortage came at a particularly bad time, since there were also shortages of an alternative antibiotic, tetracycline, at the same time. [90] The market price for doxycycline dramatically increased in the United States in 2013 and early 2014 (from $20 to over $1800 for a bottle of 500 tablets), [91] [92] [93] before decreasing again. [94] [95]

Society and culture

Brand names

Doxycycline is available worldwide under many brand names. [96]

Generic availability

Doxycycline is available as a generic medicine. [1] [14]

Research

Research reagent

Doxycycline-activated Tet-ON (tetracycline-controlled transcriptional activation) system driving inducible short hairpin RNA (shRNA) expression for controlled gene silencing via the RNA interference pathway. The Tet-ON inducible shRNA system is a regulated gene-silencing platform where short hairpin RNA (shRNA) expression is switched on only in the presence of a tetracycline-class antibiotic, such as doxycycline. Doxycycline binds to a modified Tet repressor (TetR) protein, enabling it to activate transcription from a Tet-responsive promoter, producing shRNA that is processed into small interfering RNA (siRNA) by the cell's RNA interference (RNAi) machinery. This allows researchers to precisely control the timing and level of target gene knockdown, minimizing off-target effects and enabling studies of essential genes without permanent silencing. Tet-ON inducible transgene expression cells.svg
Doxycycline-activated Tet-ON (tetracycline-controlled transcriptional activation) system driving inducible short hairpin RNA (shRNA) expression for controlled gene silencing via the RNA interference pathway. The Tet-ON inducible shRNA system is a regulated gene-silencing platform where short hairpin RNA (shRNA) expression is switched on only in the presence of a tetracycline-class antibiotic, such as doxycycline. Doxycycline binds to a modified Tet repressor (TetR) protein, enabling it to activate transcription from a Tet-responsive promoter, producing shRNA that is processed into small interfering RNA (siRNA) by the cell's RNA interference (RNAi) machinery. This allows researchers to precisely control the timing and level of target gene knockdown, minimizing off-target effects and enabling studies of essential genes without permanent silencing.

Doxycycline and other members of the tetracycline class of antibiotics are often used as research reagents in in vitro and in vivo biomedical research experiments involving bacteria as well in experiments in eukaryotic cells and organisms with inducible protein expression systems using tetracycline-controlled transcriptional activation. The mechanism of action for the antibacterial effect of tetracyclines relies on disrupting protein translation in bacteria, thereby damaging the ability of microbes to grow and repair; however protein translation is also disrupted in eukaryotic mitochondria impairing metabolism and leading to effects that can confound experimental results. [99] [100] Doxycycline is also used in "tet-on" (gene expression activated by doxycycline) and "tet-off" (gene expression inactivated by doxycycline) tetracycline-controlled transcriptional activation to regulate transgene expression in organisms and cell cultures. [101] Doxycycline is more stable than tetracycline for this purpose.[ clarification needed ] [101] At subantimicrobial doses, doxycycline is an inhibitor of matrix metalloproteases, [23] and has been used in various experimental systems for this purpose, such as for recalcitrant recurrent corneal erosions. [102]

Medical conditions

Research areas on the application of doxycycline include the following medical conditions:

Dosing

Although doxycycline is approved to treat Lyme disease, the optimal dosing and duration of treatment for this condition is a topic of ongoing research. [105] [33] it can be used in adults and children. For treatment or prophylaxis of Lyme disease in children, it can be used for a duration of up to 21 days in children of any age. [4] Doxycycline is specifically indicated to treat Lyme disease for patients presenting with erythema migrans. As for the optimal duration of treatment of this disease, guidelines vary, with some recommending a 10-day course of doxycycline, while others suggest a 14-day course; still, recent data suggest that even a 7-day course of doxycycline can be effective. Compared to other drugs, there are no significant differences in treatment response across antibiotic agents, doses, or durations when comparing 14 days versus 21 days; as such, the optimal duration of treatment of Lyme disease remains uncertain, as prolonged antibiotic courses have drawbacks, including diminishing returns in terms of patient outcomes, heightened risks of adverse events, superinfections, increased healthcare costs, and the potential for development of antibiotic resistance. Therefore, the consensus remains to treat patients with the shortest effective duration of antibiotics, as is the case with doxycycline for Lyme disease as well. [105]

Anti-inflammatory agent

Some studies show doxycycline as a potential agent to possess anti-inflammatory properties acting by inhibiting proinflammatory cytokines such as interleukin-1 (IL-1), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), and matrix metalloproteinases (MMPs) [23] while increasing the production of anti-inflammatory cytokines such as interleukin-10 (IL-10). Cytokines are small proteins that are secreted by immune cells and play a key role in the immune response. Some studies suggest that doxycycline can suppress the activation of the nuclear factor-kappa B (NF-κB) pathway, which is responsible for upregulating several inflammatory mediators in various cells, including neurons; therefore, it is studied as a potential agent for treating neuroinflammation. [106] [107] [108]

A potential explanation of doxycycline's anti-inflammatory properties is its inhibition of matrix metalloproteinases (MMPs), [23] which are a group of proteases known to regulate the turnover of extracellular matrix (ECM) and thus are suggested to be important in the process of several diseases associated with tissue remodeling and inflammation. [109] [110] [111] [112] Doxycycline has been shown to inhibit MMPs, [23] including matrilysin (MMP7), by interacting with the structural zinc atom and/or calcium atoms within the structural metal center of the protein. [113] [114] [115]

Doxycycline also inhibits allikrein-related peptidase 5 (KLK5). [112] The inhibition of MMPs and KLK5 enzymes subsequently suppresses the expression of LL-37, a cathelicidin antimicrobial peptide that, when overexpressed, can trigger inflammatory cascades. By inhibiting LL-37 expression, doxycycline helps to mitigate these downstream inflammatory cascades, thereby reducing inflammation and the symptoms of inflammatory conditions. [112]

Doxycycline is used to treat acne vulgaris and rosacea. [116] [117] [19] However, there is no clear understanding of what contributes more: the bacteriostatic properties of doxycycline, which affect bacteria (such as Propionibacterium acnes [19] ) on the surface of sebaceous glands even in lower doses called "submicrobial" [118] [119] or "subantimicrobial", [120] [121] [122] [19] or whether doxycycline's anti-inflammatory effects, which reduce inflammation in acne vulgaris and rosacea, including ocular rosacea, [42] contribute more to its therapeutic effectiveness against these skin conditions. [123] Subantimicrobial-dose doxycycline (SDD) can still have a bacteriostatic effect, especially when taken for extended periods, such as several months in treating acne and rosacea. [124] While the SDD is believed to have anti-inflammatory effects rather than solely antibacterial effects, SDD was proven to work by reducing inflammation associated with acne and rosacea. Still, the exact mechanisms have yet to be fully discovered. [125] One probable mechanism is doxycycline's ability to decrease the amount of reactive oxygen species (ROS). Inflammation in rosacea may be associated with increased production of ROS by inflammatory cells; these ROS contribute toward exacerbating symptoms. Doxycycline may reduce ROS levels and induce antioxidant activity because it directly scavenges hydroxyl radicals and singlet oxygen, helping minimize tissue damage caused by highly oxidative and inflammatory conditions. [126] Studies have shown that SDD can effectively improve acne and rosacea symptoms, [127] probably without inducing antibiotic resistance. [128] It is observed that doxycycline exerts its anti-inflammatory effects by inhibiting neutrophil chemotaxis and oxidative bursts, which are common mechanisms involved in inflammation and ROS activity in rosacea and acne. [23]

Doxycycline's dual benefits as an antibacterial and anti-inflammatory make it a helpful treatment option for diseases involving inflammation not only of the skin, such as rosacea and acne, but also in conditions such as osteoarthritis or periodontitis. [129] Nevertheless, current results are inconclusive, and evidence of doxycycline's anti-inflammatory properties needs to be improved, considering conflicting reports from animal models so far. [130] [131] [132] Doxycycline has been studied in various immunological disorders, including rheumatoid arthritis, lupus, and periodontitis. [133] In these conditions, doxycycline has been researched to determine anti-inflammatory and immunomodulatory effects that could be beneficial in treating these conditions. However, a solid conclusion still needs to be provided. [134] [135] [136] [137]

Doxycycline is also studied for its neuroprotective properties which are associated with antioxidant, anti-apoptotic, and anti-inflammatory mechanisms. In this context, it is important to note that doxycycline is able to cross the blood–brain barrier. Several studies have shown that doxycycline inhibits dopaminergic neurodegeneration through the upregulation of axonal and synaptic proteins. [138] [139] Axonal degeneration and synaptic loss are key events at the early stages of neurodegeneration and precede neuronal death in neurodegenerative diseases, including Parkinson's disease (PD). Therefore, the regeneration of the axonal and synaptic network might be beneficial in PD. [140] It has been demonstrated that doxycycline mimics nerve growth factor (NGF) signaling in PC12 cells. However, the involvement of this mechanism in the neuroprotective effect of doxycycline is unknown. Doxycycline is also studied in reverting inflammatory changes related to depression. [121] While there is some research on the use of doxycycline for treating major depressive disorder, the results are mixed. [121] [141] [142]

After a large-scale trial showed no benefit of using doxycycline in treating COVID‑19, the UK's National Institute for Health and Care Excellence (NICE) updated its guidance to not recommend the medication for the treatment of COVID‑19. [143] [144] Doxycycline was expected to possess anti-inflammatory properties that could lessen the cytokine storm associated with a SARS-CoV-2 infection, but the trials did not demonstrate the expected benefit. [145] Researchers also believed that doxycycline possesses anti-inflammatory and immunomodulatory effects that could reduce the production of cytokines in COVID-19, but these supposed effects failed to improve the outcome of COVID-19 treatment. [146] [147]

Wound healing

Research on novel drug formulations for the delivery of doxycycline in wound treatment is expanding, focusing on overcoming stability limitations for long-term storage and developing consumer-friendly, parenteral antibiotic delivery systems. The most common and practical form of doxycycline delivery is through wound dressings, which have evolved from mono- to three-layered systems to maximize healing effectiveness. [148]

Research directions on the use of doxycycline in wound healing include the continuous stabilization of doxycycline, scaling up technology and industrial production, and exploring non-contact wound treatment methods like sprays and aerosols for use in emergencies and when medical care is not readily accessible. [148]

References

  1. 1 2 3 4 5 6 7 8 9 10 "Doxycycline calcium". The American Society of Health-System Pharmacists. Archived from the original on 23 September 2015. Retrieved 18 August 2015.
  2. ↑ "Malaria". Fit for Travel. Public Health Scotland. Chemoprophylaxis. Archived from the original on 4 December 2023. Retrieved 4 December 2023.
  3. ↑ "Choosing a Drug to Prevent Malaria". Centers for Disease Control and Prevention. February 2023. Doxycycline. Archived from the original on 13 November 2016. Retrieved 4 December 2023.
  4. 1 2 Taylor-Salmon E, Shapiro ED (April 2024). "Tick-borne infections in children in North America". Curr Opin Pediatr. 36 (2): 156–163. doi:10.1097/MOP.0000000000001326. PMC   10932821 . PMID   38167816.
  5. 1 2 Schutze GE, Regan J, Bradley J (1 July 2010). "Use doxycycline as first-line treatment for rickettsial diseases". AAP News. American Academy of Pediatrics. ISSN   1556-3332. Archived from the original on 5 February 2024. Retrieved 5 February 2024.
  6. 1 2 3 Nelson ML, Levy SB (December 2011). "The history of the tetracyclines". Annals of the New York Academy of Sciences. 1241 (1): 17–32. Bibcode:2011NYASA1241...17N. doi:10.1111/j.1749-6632.2011.06354.x. PMID   22191524. S2CID   34647314.
  7. ↑ McFadden GI (March 2014). "Apicoplast". Current Biology. 24 (7): R262-3. Bibcode:2014CBio...24.R262M. doi: 10.1016/j.cub.2014.01.024 . PMID   24698369.
  8. ↑ Schlagenhauf-Lawlor P (2008). Travelers' Malaria. PMPH-USA. p. 148. ISBN   978-1-55009-336-0.
  9. 1 2 Bachmann LH, Barbee LA, Chan P, Reno H, Workowski KA, Hoover K, et al. (June 2024). "CDC Clinical Guidelines on the Use of Doxycycline Postexposure Prophylaxis for Bacterial Sexually Transmitted Infection Prevention, United States, 2024". MMWR Recommendations and Reports. 73 (RR-2): 1–8. doi:10.15585/mmwr.rr7302a1. PMC   11166373 . PMID   38833414.
  10. 1 2 Luetkemeyer AF, Donnell D, Dombrowski JC, Cohen S, Grabow C, Brown CE, et al. (April 2023). "Postexposure Doxycycline to Prevent Bacterial Sexually Transmitted Infections". New England Journal of Medicine. 388 (14): 1296–1306. doi:10.1056/NEJMoa2211934. PMC   10140182 . PMID   37018493.
  11. ↑ Fischer J, Ganellin CR (2006). Analogue-based Drug Discovery. John Wiley & Sons. p. 489. ISBN   978-3-527-60749-5.
  12. ↑ Corey EJ (2013). Drug discovery practices, processes, and perspectives. Hoboken, N.J.: John Wiley & Sons. p. 406. ISBN   978-1-118-35446-9. Archived from the original on 14 January 2023. Retrieved 9 September 2017.
  13. ↑ World Health Organization (2023). The selection and use of essential medicines 2023: web annex A: World Health Organization model list of essential medicines: 23rd list (2023). Geneva: World Health Organization. hdl: 10665/371090 . WHO/MHP/HPS/EML/2023.02.
  14. 1 2 Hamilton RJ (2011). Tarascon pharmacopoeia (12th ed.). Sudbury, MA: Jones & Bartlett Learning. p. 79. ISBN   978-1-4496-0067-9.
  15. ↑ "Top 300 of 2023". ClinCalc. Archived from the original on 12 August 2025. Retrieved 12 August 2025.
  16. ↑ "Doxycycline Drug Usage Statistics, United States, 2014 - 2023". ClinCalc. Retrieved 17 August 2025.
  17. ↑ Sweet RL, Schachter J, Landers DV, Ohm-Smith M, Robbie MO (March 1988). "Treatment of hospitalized patients with acute pelvic inflammatory disease: comparison of cefotetan plus doxycycline and cefoxitin plus doxycycline". American Journal of Obstetrics and Gynecology. 158 (3 Pt 2): 736–41. doi:10.1016/S0002-9378(16)44537-0. PMID   3162653.
  18. ↑ Gjønnaess H, Holten E (1978). "Doxycycline (Vibramycin) in pelvic inflammatory disease". Acta Obstetricia et Gynecologica Scandinavica. 57 (2): 137–9. doi:10.3109/00016347809155893. PMID   345730. S2CID   28328073.
  19. 1 2 3 4 5 6 7 8 9 Holmes NE, Charles PG (5 January 2009). "Safety and Efficacy Review of Doxycycline". Clinical Medicine. Therapeutics. 1 CMT.S2035. doi: 10.4137/CMT.S2035 . S2CID   58790579.
  20. ↑ Määttä M, Kari O, Tervahartiala T, Peltonen S, Kari M, Saari M, et al. (August 2006). "Tear fluid levels of MMP-8 are elevated in ocular rosacea--treatment effect of oral doxycycline". Graefe's Archive for Clinical and Experimental Ophthalmology = Albrecht von Graefes Archiv für Klinische und Experimentelle Ophthalmologie. 244 (8): 957–62. doi:10.1007/s00417-005-0212-3. PMID   16411105. S2CID   20540747.
  21. ↑ Quarterman MJ, Johnson DW, Abele DC, Lesher JL, Hull DS, Davis LS (January 1997). "Ocular rosacea. Signs, symptoms, and tear studies before and after treatment with doxycycline". Archives of Dermatology. 133 (1): 49–54. doi:10.1001/archderm.133.1.49. PMID   9006372.
  22. ↑ Walker DH, Paddock CD, Dumler JS (November 2008). "Emerging and re-emerging tick-transmitted rickettsial and ehrlichial infections". The Medical Clinics of North America. 92 (6): 1345–61, x. doi:10.1016/j.mcna.2008.06.002. PMID   19061755.
  23. 1 2 3 4 5 6 7 Lee JJ, Chien AL (May 2024). "Rosacea in Older Adults and Pharmacologic Treatments". Drugs Aging. 41 (5): 407–421. doi:10.1007/s40266-024-01115-y. PMID   38649625.
  24. ↑ "Doxycycline spectrum of bacterial susceptibility and Resistance" (PDF). Archived from the original (PDF) on 1 February 2014. Retrieved 4 May 2012.
  25. ↑ Stoddard RA, Galloway RL, Guerra MA (10 July 2015). "Leptospirosis". Yellow Book. Atlanta, GA: Centers for Disease Control and Prevention. Archived from the original on 9 April 2017. Retrieved 16 April 2017.
  26. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 "Doxycycline, ANDA no. 065055 Label" (PDF). U.S. Food and Drug Administration. 14 December 2012. Archived from the original (PDF) on 19 April 2014.
  27. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 "Doxycycline, ANDA no. 065454 Label" (PDF). U.S. Food and Drug Administration. 16 July 2008. Archived from the original (PDF) on 19 October 2013.
  28. ↑ Gupta N, Boodman C, Jouego CG, Van Den Broucke S (December 2023). "Doxycycline vs azithromycin in patients with scrub typhus: a systematic review of literature and meta-analysis". BMC Infect Dis. 23 (1) 884. doi: 10.1186/s12879-023-08893-7 . PMC   10726538 . PMID   38110855.
  29. ↑ Anderson A, Bijlmer H, Fournier PE, Graves S, Hartzell J, Kersh GJ, et al. (March 2013). "Diagnosis and management of Q fever, United States, 2013: recommendations from CDC and the Q Fever Working Group". MMWR. Recommendations and Reports. 62 (RR-03): 1–30. PMID   23535757. Archived from the original on 19 April 2014.
  30. ↑ Biggs HM, Behravesh CB, Bradley KK, Dahlgren FS, Drexler NA, Dumler JS, et al. (2016). "Diagnosis and Management of Tickborne Rickettsial Diseases: Rocky Mountain Spotted Fever and Other Spotted Fever Group Rickettsioses, Ehrlichioses, and Anaplasmosis — United States". MMWR. Recommendations and Reports. 65 (2): 1–44. doi: 10.15585/mmwr.rr6502a1 . PMID   27172113. Archived from the original on 28 January 2023. Retrieved 5 February 2024.
  31. ↑ "Spotted fever group rickettsial disease | DermNet". 26 October 2023. Archived from the original on 5 February 2024. Retrieved 5 February 2024.
  32. ↑ Okada T, Morozumi M, Tajima T, Hasegawa M, Sakata H, Ohnari S, et al. (December 2012). "Rapid effectiveness of minocycline or doxycycline against macrolide-resistant Mycoplasma pneumoniae infection in a 2011 outbreak among Japanese children". Clinical Infectious Diseases. 55 (12): 1642–9. doi:10.1093/cid/cis784. PMID   22972867.
  33. 1 2 "Lyme disease. Treatment". 21 December 2018. Archived from the original on 10 June 2016.
  34. ↑ U.S. Centers for Disease Control and Prevention (23 April 2025). "Leptospirosis". CDC Yellow Book: Health Information for International Travel . Retrieved 31 July 2025. For patients with mild symptoms, doxycycline is a drug of choice, unless contraindicated; alternative options include ampicillin, amoxicillin, or azithromycin.
  35. ↑ Wang S, Dunn N (10 September 2024). "Leptospirosis". StatPearls. StatPearls Publishing. PMID   28722888 . Retrieved 31 July 2025. In outpatient cases, antibiotics that may be used include doxycycline, amoxicillin, or ampicillin.
  36. ↑ U.S. Centers for Disease Control and Prevention (30 January 2018). "LEPTOSPIROSIS Fact Sheet for Clinicians" (PDF). p. 2. Retrieved 31 July 2025. For patients with mild symptoms, doxycycline is the drug of choice (100 mg orally, twice daily), if not contraindicated.
  37. ↑ Garner SE, Eady A, Bennett C, Newton JN, Thomas K, Popescu CM, et al. (Cochrane Skin Group) (August 2012). "Minocycline for acne vulgaris: efficacy and safety". The Cochrane Database of Systematic Reviews. 2012 (8) CD002086. doi:10.1002/14651858.CD002086.pub2. PMC   7017847 . PMID   22895927.
  38. 1 2 "Doxycycline Dosage Guide + Max Dose, Adjustments". Archived from the original on 5 February 2024. Retrieved 5 February 2024.
  39. ↑ Sgolastra F, Petrucci A, Gatto R, Giannoni M, Monaco A (November 2011). "Long-term efficacy of subantimicrobial-dose doxycycline as an adjunctive treatment to scaling and root planing: a systematic review and meta-analysis". Journal of Periodontology. 82 (11): 1570–1581. doi:10.1902/jop.2011.110026. PMID   21417590.
  40. ↑ van Zuuren EJ, Fedorowicz Z, Carter B, van der Linden MM, Charland L, et al. (Cochrane Skin Group) (April 2015). "Interventions for rosacea". The Cochrane Database of Systematic Reviews. 2015 (4) CD003262. doi:10.1002/14651858.CD003262.pub5. PMC   6481562 . PMID   25919144.
  41. ↑ Cao H, Yang G, Wang Y, Liu JP, Smith CA, Luo H, et al. (Cochrane Skin Group) (January 2015). "Complementary therapies for acne vulgaris". The Cochrane Database of Systematic Reviews. 1 (1) CD009436. doi:10.1002/14651858.CD009436.pub2. PMC   4486007 . PMID   25597924.
  42. 1 2 Avraham S, Khaslavsky S, Kashetsky N, Starkey SY, Zaslavsky K, Lam JM, et al. (February 2024). "Therapie der okulären Rosazea: Eine systematische Literatur-Übersicht: Treatment of ocular rosacea: a systematic review". J Dtsch Dermatol Ges. 22 (2): 167–176. doi: 10.1111/ddg.15290_g . PMID   38361192.
  43. ↑ Stewart J (21 December 2023). "Doxycycline Prophylaxis to Prevent Sexually Transmitted Infections in Women". New England Journal of Medicine. 389 (25): 2331–2340. doi:10.1056/NEJMoa2304007. PMC   10805625 . PMID   38118022.
  44. ↑ Cornelisse VJ, Riley B, Medland NA (April 2024). "Australian consensus statement on doxycycline post-exposure prophylaxis (doxy-PEP) for the prevention of syphilis, chlamydia and gonorrhoea among gay, bisexual and other men who have sex with men". Med J Aust. 220 (7): 381–386. doi: 10.5694/mja2.52258 . PMID   38479437.
  45. ↑ Vanbaelen T, Manoharan-Basil SS, Kenyon C (April 2024). "45 years of tetracycline post exposure prophylaxis for STIs and the risk of tetracycline resistance: a systematic review and meta-analysis". BMC Infect Dis. 24 (1) 376. doi: 10.1186/s12879-024-09275-3 . PMC   10996150 . PMID   38575877.
  46. ↑ Hashemi SH, Gachkar L, Keramat F, Mamani M, Hajilooi M, Janbakhsh A, et al. (April 2012). "Comparison of doxycycline-streptomycin, doxycycline-rifampin, and ofloxacin-rifampin in the treatment of brucellosis: a randomized clinical trial". International Journal of Infectious Diseases. 16 (4): e247–e251. doi: 10.1016/j.ijid.2011.12.003 . PMID   22296864.
  47. ↑ "Doryx- doxycycline hyclate tablet, delayed release". DailyMed. 23 October 2020. Archived from the original on 3 January 2022. Retrieved 5 March 2022.
  48. ↑ "Malaria - Chapter 3 - 2018 Yellow Book | Travelers' Health | CDC". U.S. Centers for Disease Control and Prevention (CDC). Archived from the original on 3 December 2018. Retrieved 4 December 2018.
  49. ↑ Dahl EL, Shock JL, Shenai BR, Gut J, DeRisi JL, Rosenthal PJ (September 2006). "Tetracyclines specifically target the apicoplast of the malaria parasite Plasmodium falciparum". Antimicrobial Agents and Chemotherapy. 50 (9): 3124–31. doi:10.1128/AAC.00394-06. PMC   1563505 . PMID   16940111.
  50. ↑ Holmes NE, Charles PG (2009). "Safety and Efficacy Review of Doxycycline". Clinical Medicine. Therapeutics. 1 CMT.S2035. doi: 10.4137/CMT.S2035 .
  51. ↑ Gaillard T, Madamet M, Pradines B (November 2015). "Tetracyclines in malaria". Malar J. 14 445. doi: 10.1186/s12936-015-0980-0 . PMC   4641395 . PMID   26555664.
  52. ↑ Guidelines for the treatment of malaria. Geneva: World Health Organization. 2015. p. 246. ISBN   978-92-4-154912-7.
  53. ↑ Portela CS, Mendes de Araújo CP, Moura Sousa P, Gomes Simão CL, Silva de Oliveira JC, Crainey JL (2024). "Filarial disease in the Brazilian Amazon and emerging opportunities for treatment and control". Current Research in Parasitology & Vector-borne Diseases. 5 100168. doi:10.1016/j.crpvbd.2023.100168. PMC   10821485 . PMID   38283060.
  54. ↑ Hoerauf A, Mand S, Fischer K, Kruppa T, Marfo-Debrekyei Y, Debrah AY, et al. (November 2003). "Doxycycline as a novel strategy against bancroftian filariasis-depletion of Wolbachia endosymbionts from Wuchereria bancrofti and stop of microfilaria production". Medical Microbiology and Immunology. 192 (4): 211–6. doi:10.1007/s00430-002-0174-6. PMID   12684759. S2CID   23349595.
  55. ↑ Taylor MJ, Makunde WH, McGarry HF, Turner JD, Mand S, Hoerauf A (2005). "Macrofilaricidal activity after doxycycline treatment of Wuchereria bancrofti: a double-blind, randomised placebo-controlled trial". Lancet. 365 (9477): 2116–21. doi:10.1016/S0140-6736(05)66591-9. PMID   15964448. S2CID   21382828.
  56. 1 2 3 4 "Doxycycline hyclate Susceptibility and Minimum Inhibitory Concentration (MIC) Data" (PDF). toku-e.com. Archived (PDF) from the original on 24 February 2015. Retrieved 16 April 2017.
  57. ↑ Kaufman JA, Lee MJ (22 June 2013). Vascular and interventional radiology (2nd ed.). Philadelphia, PA: Saunders. ISBN   978-0-323-07672-2. OCLC   853455295.
  58. ↑ Muller M, Butler J, Heidecker B (7 January 2020). "Emerging therapies in transthyretin amyloidosis - a new wave of hope after years of stagnancy?". European Journal of Heart Failure. 22 (1). Wiley: 39–53. doi: 10.1002/ejhf.1695 . PMID   31912620.
  59. 1 2 3 4 Haberfeld H, ed. (2020). Austria-Codex (in German). Vienna: Österreichischer Apothekerverlag. Doxycyclin Genericon 200 mg lösliche Tabletten.
  60. ↑ PubMed Health (1 July 2016). "Doxycycline (By mouth)". U.S. National Library of Medicine. Archived from the original on 11 November 2013. Retrieved 16 July 2016.
  61. ↑ Chung AM, Reed MD, Blumer JL (2002). "Antibiotics and breast-feeding: a critical review of the literature". Paediatric Drugs. 4 (12): 817–37. doi:10.2165/00128072-200204120-00006. PMID   12431134. S2CID   8595370.
  62. ↑ Mylonas I (January 2011). "Antibiotic chemotherapy during pregnancy and lactation period: aspects for consideration". Archives of Gynecology and Obstetrics. 283 (1): 7–18. doi:10.1007/s00404-010-1646-3. PMID   20814687. S2CID   25492353.
  63. ↑ "Bioterrorism and Drug Preparedness - Doxycycline Use by Pregnant and Lactating Women". FDA. 3 November 2018. Archived from the original on 8 February 2019. Retrieved 9 December 2018.
  64. ↑ Gaillard T, Briolant S, Madamet M, Pradines B (April 2017). "The end of a dogma: the safety of doxycycline use in young children for malaria treatment". Malaria Journal. 16 (1) 148. doi: 10.1186/s12936-017-1797-9 . PMC   5390373 . PMID   28407772.
  65. 1 2 Hitchings A, Lonsdale D, Burrage D, Baker E (2015). Top 100 drugs: clinical pharmacology and practical prescribing. Churchill Livingstone. pp. 200–201. ISBN   978-0-7020-5516-4.
  66. 1 2 Riond JL, Riviere JE (October 1988). "Pharmacology and toxicology of doxycycline". Veterinary and Human Toxicology. 30 (5): 431–43. PMID   3055652.
  67. ↑ Affolter K, Samowitz W, Boynton K, Kelly ED (August 2017). "Doxycycline-induced gastrointestinal injury". Human Pathology. 66: 212–215. doi:10.1016/j.humpath.2017.02.011. PMID   28286288.
  68. ↑ Hung YP, Lee JC, Lin HJ, Liu HC, Wu YH, Tsai PJ, et al. (June 2015). "Doxycycline and Tigecycline: Two Friendly Drugs with a Low Association with Clostridium Difficile Infection". Antibiotics. 4 (2): 216–29. doi: 10.3390/antibiotics4020216 . PMC   4790331 . PMID   27025622.
  69. ↑ Tan KR, Magill AJ, Parise ME, Arguin PM (April 2011). "Doxycycline for malaria chemoprophylaxis and treatment: report from the CDC expert meeting on malaria chemoprophylaxis". The American Journal of Tropical Medicine and Hygiene. 84 (4): 517–31. doi:10.4269/ajtmh.2011.10-0285. PMC   3062442 . PMID   21460003.
  70. 1 2 Dréno B, Bettoli V, Ochsendorf F, Layton A, Mobacken H, Degreef H (November–December 2004). "European recommendations on the use of oral antibiotics for acne". European Journal of Dermatology. 14 (6): 391–9. PMID   15564203. Archived from the original on 17 August 2011.
  71. ↑ Lee TW, Russell L, Deng M, Gibson PR (August 2013). "Association of doxycycline use with the development of gastroenteritis, irritable bowel syndrome and inflammatory bowel disease in Australians deployed abroad". Internal Medicine Journal. 43 (8): 919–26. doi:10.1111/imj.12179. PMID   23656210. S2CID   9418654.
  72. ↑ Margolis DJ, Fanelli M, Hoffstad O, Lewis JD (December 2010). "Potential association between the oral tetracycline class of antimicrobials used to treat acne and inflammatory bowel disease". The American Journal of Gastroenterology. 105 (12): 2610–6. doi:10.1038/ajg.2010.303. PMID   20700115. S2CID   20085592.
  73. ↑ Archer JS, Archer DF (June 2002). "Oral contraceptive efficacy and antibiotic interaction: a myth debunked". Journal of the American Academy of Dermatology. 46 (6): 917–23. doi:10.1067/mjd.2002.120448. PMID   12063491.
  74. ↑ DeRossi SS, Hersh EV (October 2002). "Antibiotics and oral contraceptives". Dental Clinics of North America. 46 (4): 653–64. CiteSeerX   10.1.1.620.9933 . doi:10.1016/S0011-8532(02)00017-4. PMID   12436822.
  75. ↑ Flower R, Rang HP, Dale MM, Ritter JM, Henderson G (2012). Rang & Dale's Pharmacology. Edinburgh: Churchill Livingstone. ISBN   978-0-7020-3471-8.
  76. 1 2 Maaland MG, Papich MG, Turnidge J, Guardabassi L (November 2013). "Pharmacodynamics of doxycycline and tetracycline against Staphylococcus pseudintermedius: proposal of canine-specific breakpoints for doxycycline". Journal of Clinical Microbiology. 51 (11): 3547–54. doi:10.1128/JCM.01498-13. PMC   3889732 . PMID   23966509.
  77. ↑ Agwuh KN, MacGowan A (August 2006). "Pharmacokinetics and pharmacodynamics of the tetracyclines including glycylcyclines". The Journal of Antimicrobial Chemotherapy. 58 (2): 256–65. doi:10.1093/jac/dkl224. PMID   16816396.
  78. ↑ "Doxycycline". www.drugbank.ca. Archived from the original on 10 November 2008. Retrieved 23 January 2019.
  79. 1 2 3 4 5 Dinnendahl, V, Fricke, U, eds. (2010). Arzneistoff-Profile (in German). Vol. 4 (24 ed.). Eschborn, Germany: Govi Pharmazeutischer Verlag. Doxycyclin. ISBN   978-3-7741-9846-3.
  80. 1 2 Doxycycline Professional Drug Facts . Accessed 5 August 2020.
  81. ↑ Haberfeld H, ed. (2020). Austria-Codex (in German). Vienna: Österreichischer Apothekerverlag. Minostad 50 mg-Kapseln.
  82. ↑ "Principles and methods for the assessment of nephrotoxicity associated with exposure to chemicals". Environmental health criteria. Vol. 119. World Health Organization (WHO). 1991. ISBN   92-4-157119-5. ISSN   0250-863X. Archived from the original on 10 May 2011.
  83. 1 2 Williams DA, Foye WO, Lemke TL (2008). Foye's Principles of Medicinal Chemistry (6th ed.). Lippincott Williams & Wilkins. ISBN   978-0-7817-6879-5.
  84. 1 2 Brunton LL, Chabner BA, Knollmann BC (eds.). Goodman & Gilman's The Pharmacological Basis of Therapeutics (12th ed.).
  85. ↑ "Pfizer, Inc. v. International Rectifier Corp., 545 F. Supp. 486 (C.D. Cal. 1980)". Justia Law. Archived from the original on 24 February 2015.
  86. 1 2 "Pfizer to Get Rachelle Units". The New York Times. The Associated Press. 6 July 1983. Archived from the original on 6 March 2016.
  87. ↑ "Nationwide Shortage of Doxycycline: Resources for Providers and Recommendations for Patient Care". CDC Health Alert Network. 12 June 2013. Archived from the original on 15 February 2015.
  88. ↑ "Doxycycline Capsules and Tablets". American Society of Health-System Pharmacists. 12 December 2014. Archived from the original on 1 January 2015.
  89. ↑ "Doxycycline Hyclate Injection". American Society of Health-System Pharmacists. 12 November 2014. Archived from the original on 1 January 2015.
  90. ↑ "FDA reports shortage of doxycycline antibiotic. What are your options?". Consumer Reports News. 4 February 2013. Archived from the original on 1 January 2015.
  91. ↑ Frio A (12 March 2013). "Sudden increase in cost of common drug concerns many". WSMV-TV . Archived from the original on 31 December 2014.
  92. ↑ Rosenthal E (7 October 2014). "Officials Question the Rising Costs of Generic Drugs". The New York Times . Archived from the original on 23 February 2017.
  93. ↑ Palmer E (13 March 2014). "Hikma hits the jackpot with doxycycline shortage". FiercePharmaManufacturing. Archived from the original on 1 January 2015.
  94. ↑ "Costco Drug Information". Archived from the original on 4 March 2016. Retrieved 31 July 2016.
  95. ↑ "Doxycycline Hyclate Prices and Doxycycline Hyclate Coupons". GoodRx. Archived from the original on 28 July 2016. Retrieved 31 July 2016.
  96. ↑ "International availability for doxycycline". drugs.com. Archived from the original on 16 May 2015. Retrieved 29 April 2015.
  97. ↑ Das AT, Tenenbaum L, Berkhout B (2016). "Tet-On Systems For Doxycycline-inducible Gene Expression". Curr Gene Ther. 16 (3): 156–67. doi:10.2174/1566523216666160524144041. PMC   5070417 . PMID   27216914.
  98. ↑ Siddiqui M, Tous C, Wong WW (December 2022). "Small molecule-inducible gene regulatory systems in mammalian cells: progress and design principles". Curr Opin Biotechnol. 78 102823. doi:10.1016/j.copbio.2022.102823. PMC   9951109 . PMID   36332343.
  99. ↑ Moullan N, Mouchiroud L, Wang X, Ryu D, Williams EG, Mottis A, et al. (March 2015). "Tetracyclines Disturb Mitochondrial Function across Eukaryotic Models: A Call for Caution in Biomedical Research". Cell Reports. 10 (10): 1681–1691. doi:10.1016/j.celrep.2015.02.034. PMC   4565776 . PMID   25772356.
  100. ↑ Chatzispyrou IA, Held NM, Mouchiroud L, Auwerx J, Houtkooper RH (November 2015). "Tetracycline antibiotics impair mitochondrial function and its experimental use confounds research". Cancer Research. 75 (21): 4446–9. doi:10.1158/0008-5472.CAN-15-1626. PMC   4631686 . PMID   26475870.
  101. 1 2 Gossen M, Freundlieb S, Bender G, Müller G, Hillen W, Bujard H (June 1995). "Transcriptional activation by tetracyclines in mammalian cells". Science. 268 (5218): 1766–9. Bibcode:1995Sci...268.1766G. doi:10.1126/science.7792603. PMID   7792603.
  102. ↑ Dursun D, Kim MC, Solomon A, Pflugfelder SC (July 2001). "Treatment of recalcitrant recurrent corneal erosions with inhibitors of matrix metalloproteinase-9, doxycycline and corticosteroids". American Journal of Ophthalmology. 132 (1): 8–13. doi:10.1016/S0002-9394(01)00913-8. PMID   11438047.
  103. ↑ Leung E, Landa G (September 2013). "Update on current and future novel therapies for dry age-related macular degeneration". Expert Review of Clinical Pharmacology. 6 (5): 565–79. doi:10.1586/17512433.2013.829645. PMID   23971874. S2CID   26680094.
  104. ↑ Greenwald RA (December 2011). "The road forward: the scientific basis for tetracycline treatment of arthritic disorders". Pharmacological Research. 64 (6): 610–3. doi:10.1016/j.phrs.2011.06.010. PMID   21723947.
  105. 1 2 Roca Mora MM, Cunha LM, Godoi A, Donadon I, Clemente M, Marcolin P, et al. (June 2024). "Shorter versus longer duration of antimicrobial therapy for early Lyme disease: A systematic review and meta-analysis". Diagn Microbiol Infect Dis. 109 (2) 116215. doi:10.1016/j.diagmicrobio.2024.116215. PMID   38493509.
  106. ↑ Singh S, Khanna D, Kalra S (2021). "Minocycline and Doxycycline: More Than Antibiotics" . Curr Mol Pharmacol. 14 (6): 1046–1065. doi:10.2174/1874467214666210210122628. PMID   33568043. S2CID   231881758. Archived from the original on 2 February 2024. Retrieved 2 February 2024.
  107. ↑ Henehan M, Montuno M, De Benedetto A (November 2017). "Doxycycline as an anti-inflammatory agent: updates in dermatology". Journal of the European Academy of Dermatology and Venereology. 31 (11): 1800–1808. doi:10.1111/jdv.14345. PMID   28516469. S2CID   37723341.
  108. ↑ Berman B, Perez OA, Zell D (January 2007). "Update on rosacea and anti-inflammatory-dose doxycycline". Drugs of Today. 43 (1): 27–34. doi:10.1358/dot.2007.43.1.1025697. PMID   17315050.
  109. ↑ Lagente V, Victoni T, Boichot E (2011). "Matrix Metalloproteinase Inhibitors as New Anti-inflammatory Drugs". Proteases and Their Receptors in Inflammation. Progress in Inflammation Research. Springer. pp. 101–122. doi:10.1007/978-3-0348-0157-7_5. ISBN   978-3-0348-0156-0.
  110. ↑ Wang S, Liu C, Liu X, He Y, Shen D, Luo Q, et al. (October 2017). "Effects of matrix metalloproteinase inhibitor doxycycline and CD147 antagonist peptide-9 on gallbladder carcinoma cell lines". Tumour Biol. 39 (10) 1010428317718192. doi: 10.1177/1010428317718192 . PMID   29034777. S2CID   206614670.
  111. ↑ Jung JJ, Razavian M, Kim HY, Ye Y, Golestani R, Toczek J, et al. (September 2016). "Matrix metalloproteinase inhibitor, doxycycline and progression of calcific aortic valve disease in hyperlipidemic mice". Sci Rep. 6 32659. Bibcode:2016NatSR...632659J. doi:10.1038/srep32659. PMC   5020643 . PMID   27619752.
  112. 1 2 3 Wehrli JM, Xia Y, Offenhammer B, Kleim B, Müller D, Bach DR (February 2023). "Effect of the Matrix Metalloproteinase Inhibitor Doxycycline on Human Trace Fear Memory". eNeuro. 10 (2). doi:10.1523/ENEURO.0243-22.2023. PMC   9961363 . PMID   36759188.
  113. ↑ Liu J, Xiong W, Baca-Regen L, Nagase H, Baxter BT (December 2003). "Mechanism of inhibition of matrix metalloproteinase-2 expression by doxycycline in human aortic smooth muscle cells". J Vasc Surg. 38 (6): 1376–83. doi:10.1016/s0741-5214(03)01022-x. PMID   14681644.
  114. ↑ García RA, Pantazatos DP, Gessner CR, Go KV, Woods VL, Villarreal FJ (April 2005). "Molecular interactions between matrilysin and the matrix metalloproteinase inhibitor doxycycline investigated by deuterium exchange mass spectrometry". Mol Pharmacol. 67 (4): 1128–36. doi:10.1124/mol.104.006346. PMID   15665254. S2CID   23253029.
  115. ↑ Liu J, Khalil RA (2017). "Matrix Metalloproteinase Inhibitors as Investigational and Therapeutic Tools in Unrestrained Tissue Remodeling and Pathological Disorders". Prog Mol Biol Transl Sci. Progress in Molecular Biology and Translational Science. 148: 355–420. doi:10.1016/bs.pmbts.2017.04.003. ISBN   978-0-12-812776-6. PMC   5548434 . PMID   28662828.
  116. ↑ Eichenfield DZ, Sprague J, Eichenfield LF (November 2021). "Management of Acne Vulgaris: A Review". JAMA. 326 (20): 2055–2067. doi:10.1001/jama.2021.17633. PMID   34812859. S2CID   244490539.
  117. ↑ Baldwin H (September 2020). "Oral Antibiotic Treatment Options for Acne Vulgaris". J Clin Aesthet Dermatol. 13 (9): 26–32. PMC   7577330 . PMID   33133338.
  118. ↑ Parish LC, Parish JL, Routh HB, Witkowski JA (2005). "The treatment of acne vulgaris with low dosage doxycycline". Acta Dermatovenerol Croat. 13 (3): 156–9. PMID   16146617.
  119. ↑ Stein Gold LF (June 2016). "Acne: What's New". Semin Cutan Med Surg. 35 (6 Suppl): S114–6. doi:10.12788/j.sder.2016.036. PMID   27538054.
  120. ↑ Kontochristopoulos G, Tsiogka A, Agiasofitou E, Kapsiocha A, Soulaidopoulos S, Liakou AI, et al. (November 2022). "Efficacy of Subantimicrobial, Modified-Release Doxycycline Compared to Regular-Release Doxycycline for the Treatment of Hidradenitis Suppurativa". Skin Appendage Disord. 8 (6): 476–481. doi:10.1159/000524762. PMC   9672876 . PMID   36407641.
  121. 1 2 3 Mello BSF, Chaves Filho AJM, Custódio CS, Rodrigues PA, Carletti JV, Vasconcelos SMM, et al. (September 2021). "Doxycycline at subantimicrobial dose combined with escitalopram reverses depressive-like behavior and neuroinflammatory hippocampal alterations in the lipopolysaccharide model of depression". J Affect Disord. 292: 733–745. doi:10.1016/j.jad.2021.05.083. PMID   34161892.
  122. ↑ Bikowski JB (2003). "Subantimicrobial dose doxycycline for acne and rosacea". Skinmed. 2 (4): 234–45. doi:10.1111/j.1540-9740.2003.03014.x. PMID   14673277.
  123. ↑ Navarro-Triviño FJ, Pérez-López I, Ruiz-Villaverde R (September 2020). "Doxycycline, an Antibiotic or an Anti-Inflammatory Agent? The Most Common Uses in Dermatology". Actas Dermosifiliogr (Engl Ed). 111 (7): 561–566. doi: 10.1016/j.ad.2019.12.006 . PMID   32401726. S2CID   218635190.
  124. ↑ Zolotarev O, Khakimova A, Rahim F, Senel E, Zatsman I, Gu D (October 2023). "Scientometric analysis of trends in global research on acne treatment". Int J Womens Dermatol. 9 (3) e082. doi:10.1097/JW9.0000000000000082. PMC   10378739 . PMID   37521754.
  125. ↑ Shields A, Barbieri JS (August 2023). "From Breakouts to Bargains: Strategies for Patient-Centered, Cost-effective Acne Care". Cutis. 112 (2): E24–E29. doi: 10.12788/cutis.0844 . PMC   10951614 . PMID   37820334. S2CID   261786019.
  126. ↑ Akamatsu H, Asada M, Komura J, Asada Y, Niwa Y (1992). "Effect of doxycycline on the generation of reactive oxygen species: a possible mechanism of action of acne therapy with doxycycline". Acta Derm Venereol. 72 (3): 178–9. doi: 10.2340/0001555572178179 . PMID   1357852. S2CID   45726787.
  127. ↑ Zaenglein AL, Pathy AL, Schlosser BJ, Alikhan A, Baldwin HE, Berson DS, et al. (May 2016). "Guidelines of care for the management of acne vulgaris". J Am Acad Dermatol. 74 (5): 945–73.e33. doi:10.1016/j.jaad.2015.12.037. PMID   26897386.
  128. ↑ Wise RD (2007). "Submicrobial doxycycline and rosacea". Compr Ther. 33 (2): 78–81. doi:10.1007/s12019-007-8003-x. PMID   18004018. S2CID   28262106.
  129. ↑ Ahuja TS (August 2003). "Doxycycline decreases proteinuria in glomerulonephritis". Am J Kidney Dis. 42 (2): 376–80. doi:10.1016/s0272-6386(03)00662-0. PMID   12900822.
  130. ↑ Patel A, Khande H, Periasamy H, Mokale S (June 2020). "Immunomodulatory Effect of Doxycycline Ameliorates Systemic and Pulmonary Inflammation in a Murine Polymicrobial Sepsis Model". Inflammation. 43 (3): 1035–1043. doi:10.1007/s10753-020-01188-y. PMC   7224120 . PMID   31955291.
  131. ↑ Martin V, Bettencourt AF, Santos C, Fernandes MH, Gomes PS (September 2023). "Unveiling the Osteogenic Potential of Tetracyclines: A Comparative Study in Human Mesenchymal Stem Cells". Cells. 12 (18): 2244. doi: 10.3390/cells12182244 . PMC   10526833 . PMID   37759467.
  132. ↑ Waitayangkoon P, Moon SJ, Tirupur Ponnusamy JJ, Zeng L, Driban J, McAlindon T (September 2023). "Long-Term Safety Profiles Macrolides and Tetracyclines: A Systematic Review and Meta-analysis". J Clin Pharmacol. 64 (2): 164–177. doi:10.1002/jcph.2358. PMC   11949418 . PMID   37751595. S2CID   263151406.
  133. ↑ Orylska-Ratynska M, Placek W, Owczarczyk-Saczonek A (June 2022). "Tetracyclines-An Important Therapeutic Tool for Dermatologists". Int J Environ Res Public Health. 19 (12): 7246. doi: 10.3390/ijerph19127246 . PMC   9224192 . PMID   35742496.
  134. ↑ Santos M, Gonçalves-Santos E, Gonçalves R, Santos E, Campos C, Bastos D, et al. (May 2021). "Doxycycline aggravates granulomatous inflammation and lung microstructural remodeling induced by Schistosoma mansoni infection". Int Immunopharmacol. 94 107462. doi:10.1016/j.intimp.2021.107462. PMID   33611055. S2CID   231988574.
  135. ↑ Florou DT, Mavropoulos A, Dardiotis E, Tsimourtou V, Siokas V, Aloizou AM, et al. (2021). "Tetracyclines Diminish In Vitro IFN-γ and IL-17-Producing Adaptive and Innate Immune Cells in Multiple Sclerosis". Front Immunol. 12 739186. doi: 10.3389/fimmu.2021.739186 . PMC   8662812 . PMID   34899697.
  136. ↑ Garrido-Mesa J, Adams K, Galvez J, Garrido-Mesa N (May 2022). "Repurposing tetracyclines for acute respiratory distress syndrome (ARDS) and severe COVID-19: a critical discussion of recent publications". Expert Opin Investig Drugs. 31 (5): 475–482. doi:10.1080/13543784.2022.2054325. PMC   9115781 . PMID   35294307.
  137. ↑ de Witte LD, Munk Laursen T, Corcoran CM, Kahn RS, Birnbaum R, Munk-Olsen T, et al. (July 2023). "A Sex-Dependent Association Between Doxycycline Use and Development of Schizophrenia". Schizophr Bull. 49 (4): 953–961. doi:10.1093/schbul/sbad008. PMC   10318877 . PMID   36869773.
  138. ↑ Santa-Cecília FV, Leite CA, Del-Bel E, Raisman-Vozari R (May 2019). "The Neuroprotective Effect of Doxycycline on Neurodegenerative Diseases". Neurotox Res. 35 (4): 981–986. doi:10.1007/s12640-019-00015-z. PMID   30798507. S2CID   71147889.
  139. ↑ Paldino E, Balducci C, La Vitola P, Artioli L, D'Angelo V, Giampà C, et al. (April 2020). "Neuroprotective Effects of Doxycycline in the R6/2 Mouse Model of Huntington's Disease". Mol Neurobiol. 57 (4): 1889–1903. doi:10.1007/s12035-019-01847-8. PMC   7118056 . PMID   31879858.
  140. ↑ do Amaral L, Dos Santos NAG, Sisti FM, Del Bel E, Dos Santos AC (August 2023). "Doxycycline inhibits dopaminergic neurodegeneration through upregulation of axonal and synaptic proteins". Naunyn-Schmiedeberg's Arch Pharmacol. 396 (8): 1787–1796. doi:10.1007/s00210-023-02435-3. PMID   36843128. S2CID   257218181.
  141. ↑ Lee JW, Lee H, Kang HY (October 2021). "Association between depression and antibiotic use: analysis of population-based National Health Insurance claims data". BMC Psychiatry. 21 (1) 536. doi: 10.1186/s12888-021-03550-2 . PMC   8554858 . PMID   34711196.
  142. ↑ Leyder E, Suresh P, Jun R, Overbey K, Banerjee T, Melnikova T, et al. (February 2023). "Depression-related phenotypes at early stages of Aβ and tau accumulation in inducible Alzheimer's disease mouse model: Task-oriented and concept-driven interpretations". Behav Brain Res. 438 114187. doi:10.1016/j.bbr.2022.114187. PMID   36343696. S2CID   253300844.
  143. ↑ "Platform trial rules out treatments for COVID-19" . NIHR Evidence. 31 May 2022. doi:10.3310/nihrevidence_50873. Archived from the original on 1 June 2022. Retrieved 1 June 2022.
  144. ↑ Butler CC, Yu LM, Dorward J, Gbinigie O, Hayward G, Saville BR, et al. (September 2021). "Doxycycline for community treatment of suspected COVID-19 in people at high risk of adverse outcomes in the UK (PRINCIPLE): a randomised, controlled, open-label, adaptive platform trial". The Lancet. Respiratory Medicine. 9 (9): 1010–1020. doi:10.1016/S2213-2600(21)00310-6. PMC   8315758 . PMID   34329624.
  145. ↑ Sharma S, Bhatt P, Asdaq S, Alshammari M, Alanazi A, Alrasheedi N, et al. (May 2022). "Combined therapy with ivermectin and doxycycline can effectively alleviate the cytokine storm of COVID-19 infection amid vaccination drive: A narrative review". J Infect Public Health. 15 (5): 566–572. doi:10.1016/j.jiph.2022.03.014. PMC   8964533 . PMID   35462191.
  146. ↑ Ohe M (February 2022). "Multi-drug Treatment for COVID-19-induced Acute Respiratory Distress Syndrome". Turk J Pharm Sci. 19 (1): 101–103. doi:10.4274/tjps.galenos.2021.63060. PMC   8892560 . PMID   35227056.
  147. ↑ Dorobisz K, Dorobisz T, Janczak D, Zatoński T (2021). "Doxycycline in the Coronavirus Disease 2019 Therapy". Ther Clin Risk Manag. 17: 1023–1026. doi: 10.2147/TCRM.S314923 . PMC   8464303 . PMID   34584416.
  148. 1 2 Saliy O, Popova M, Tarasenko H, Getalo O (April 2024). "Development strategy of novel drug formulations for the delivery of doxycycline in the treatment of wounds of various etiologies". Eur J Pharm Sci. 195 106636. doi: 10.1016/j.ejps.2023.106636 . PMID   38185273.
This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.