Doxycycline is a

broad-spectrum A broad-spectrum antibiotic is an antibiotic that acts on the two major bacterial groups, Gram-positive and Gram-negative, or any antibiotic that acts against a wide range of disease-causing bacteria. These medications are used when a bacterial in ...

antibiotic An antibiotic is a type of antimicrobial substance active against bacteria. It is the most important type of antibacterial agent for fighting pathogenic bacteria, bacterial infections, and antibiotic medications are widely used in the therapy ...

of the tetracycline class used in the treatment of infections caused by

bacteria Bacteria (; : bacterium) are ubiquitous, mostly free-living organisms often consisting of one Cell (biology), biological cell. They constitute a large domain (biology), domain of Prokaryote, prokaryotic microorganisms. Typically a few micr ...

and certain

parasites Parasitism is a close relationship between species, where one organism, the parasite, lives (at least some of the time) on or inside another organism, the host, causing it some harm, and is adapted structurally to this way of life. The en ...

. It is used to treat

bacterial pneumonia Bacterial pneumonia is a type of pneumonia caused by bacterial infection. Types Gram-positive '' Streptococcus pneumoniae'' () is the most common bacterial cause of pneumonia in all age groups except newborn infants. ''Streptococcus pneumoniae ...

acne Acne ( ), also known as ''acne vulgaris'', is a long-term Cutaneous condition, skin condition that occurs when Keratinocyte, dead skin cells and Sebum, oil from the skin clog hair follicles. Typical features of the condition include comedo, ...

chlamydia infection Chlamydia, or more specifically a chlamydia infection, is a sexually transmitted infection caused by the bacterium ''Chlamydia trachomatis''. Most people who are infected have no symptoms. When symptoms do appear, they may occur only several w ...

Lyme disease Lyme disease, also known as Lyme borreliosis, is a tick-borne disease caused by species of ''Borrelia'' bacteria, Disease vector, transmitted by blood-feeding ticks in the genus ''Ixodes''. It is the most common disease spread by ticks in th ...

cholera Cholera () is an infection of the small intestine by some Strain (biology), strains of the Bacteria, bacterium ''Vibrio cholerae''. Symptoms may range from none, to mild, to severe. The classic symptom is large amounts of watery diarrhea last ...

typhus Typhus, also known as typhus fever, is a group of infectious diseases that include epidemic typhus, scrub typhus, and murine typhus. Common symptoms include fever, headache, and a rash. Typically these begin one to two weeks after exposu ...

, and

syphilis Syphilis () is a sexually transmitted infection caused by the bacterium ''Treponema pallidum'' subspecies ''pallidum''. The signs and symptoms depend on the stage it presents: primary, secondary, latent syphilis, latent or tertiary. The prim ...

. It is also used to prevent

malaria Malaria is a Mosquito-borne disease, mosquito-borne infectious disease that affects vertebrates and ''Anopheles'' mosquitoes. Human malaria causes Signs and symptoms, symptoms that typically include fever, Fatigue (medical), fatigue, vomitin ...

. Doxycycline may be taken

by mouth Oral administration is a route of administration whereby a substance is taken through the Human mouth, mouth, swallowed, and then processed via the digestive system. This is a common route of administration for many medications. Oral administ ...

or by

injection into a vein Intravenous therapy (abbreviated as IV therapy) is a medical technique that administers fluids, medications and nutrients directly into a person's vein. The intravenous route of administration is commonly used for rehydration or to provide nutr ...

. Common side effects include

diarrhea Diarrhea (American English), also spelled diarrhoea or diarrhœa (British English), is the condition of having at least three loose, liquid, or watery bowel movements in a day. It often lasts for a few days and can result in dehydration d ...

, nausea, vomiting, abdominal pain, and an increased risk of

sunburn Sunburn is a form of radiation burn that affects living tissue, such as skin, that results from an overexposure to ultraviolet (UV) radiation, usually from the Sun. Common symptoms in humans and other animals include red or reddish skin tha ...

. Use during pregnancy is not recommended. Like other agents of the tetracycline class, it either slows or kills bacteria by inhibiting protein production. It kills malaria by targeting a plastid organelle, the

apicoplast An apicoplast is a derived non-photosynthetic plastid found in most Apicomplexa, including ''Toxoplasma gondii'', and ''Plasmodium falciparum'' and other ''Plasmodium'' spp. (parasites causing malaria), but not in others such as ''Cryptosporidium' ...

Doxycycline was patented in 1957 and came into commercial use in 1967. It is on the

World Health Organization's List of Essential Medicines The WHO Model List of Essential Medicines (aka Essential Medicines List or EML), published by the World Health Organization (WHO), contains the medications considered to be most effective and safe to meet the most important needs in a health s ...

. Doxycycline is available as a

generic medicine A generic drug is a pharmaceutical drug that contains the same chemical substance as a drug that was originally protected by chemical patents. Generic drugs are allowed for sale after the patents on the original drugs expire. Because the active ch ...

. In 2022, it was the 68th most commonly prescribed medication in the United States, with more than 9million prescriptions.

Medical uses

In addition to the general indications for all members of the

tetracycline antibiotics Tetracyclines are a group of broad-spectrum antibiotic compounds that have a common basic structure and are either isolated directly from several species of ''Streptomyces'' bacteria or produced semi-synthetically from those isolated compounds. ...

group, doxycycline is frequently used to treat

, chronic

prostatitis Prostatitis is an umbrella term for a variety of medical conditions that incorporate bacterial and non-bacterial origin illnesses in the pelvic region. In contrast with the plain meaning of the word (which means "inflammation of the prostate"), the ...

sinusitis Sinusitis, also known as rhinosinusitis, is an inflammation of the mucous membranes that line the sinuses resulting in symptoms that may include production of thick nasal mucus, nasal congestion, facial congestion, facial pain, facial pressure ...

pelvic inflammatory disease Pelvic inflammatory disease (PID), also known as pelvic inflammatory disorder, is an infection of the upper part of the female reproductive system, mainly the uterus, fallopian tubes, and ovaries, and inside of the pelvis. Often, there may be no ...

, severe

rosacea Rosacea is a long-term skin condition that typically affects the face. It results in redness, pimples, swelling, and small and superficial dilated blood vessels. Often, the nose, cheeks, forehead, and chin are most involved. A red, en ...

, and

rickettsial ''Rickettsia'' is a genus of nonmotile, gram-negative, nonspore-forming, highly pleomorphic bacteria that may occur in the forms of cocci (0.1 μm in diameter), bacilli (1–4 μm long), or threads (up to about 10 μm long). The genus was na ...

infections. 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 An angiogenesis inhibitor is a substance that inhibits the growth of new blood vessels (angiogenesis). Some angiogenesis inhibitors are endogenous and a normal part of the body's control and others are obtained exogenously through pharmaceutical d ...

properties. In Canada, in 2004, doxycycline was considered a first-line treatment for

chlamydia Chlamydia, or more specifically a chlamydia infection, is a sexually transmitted infection caused by the bacterium ''Chlamydia trachomatis''. Most people who are infected have no symptoms. When symptoms do appear, they may occur only several w ...

and

non-gonococcal urethritis Nongonococcal urethritis (NGU) is inflammation of the urethra that is not caused by gonorrheal infection. For treatment purposes, doctors usually classify infectious urethritis in two categories: gonococcal urethritis, caused by gonorrhea, and ...

and with

cefixime Cefixime, sold under the brand name Suprax among others, is an antibiotic medication used to treat a number of bacterial infections. These infections include otitis media, strep throat, pneumonia, urinary tract infections, gonorrhea, and Lyme ...

for uncomplicated

gonorrhea Gonorrhoea or gonorrhea, colloquially known as the clap, is a sexually transmitted infection (STI) caused by the bacterium ''Neisseria gonorrhoeae''. Infection may involve the genitals, mouth, or rectum. Gonorrhea is spread through sexual c ...

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 ''Moraxella catarrhalis'' is a fastidious, nonmotile, Gram-negative, aerobic, oxidase-positive diplococcus that can cause infections of the respiratory system, middle ear, eye, central nervous system, and joints of humans. It causes the in ...

'', ''

Brucella melitensis ''Brucella melitensis'' is a Gram-negative coccobacillus bacterium from the Brucellaceae family. The bacterium causes ovine brucellosis, along with '' Brucella ovis''. Humans can become infected if they have contact with an infected animal or its ...

'', ''

Chlamydia pneumoniae Chlamydia, or more specifically a chlamydia infection, is a sexually transmitted infection caused by the bacterium ''Chlamydia trachomatis''. Most people who are infected have no symptoms. When symptoms do appear, they may occur only several w ...

'', and ''

Mycoplasma pneumoniae ''Mycoplasma pneumoniae'' is a species of very small-cell bacteria that lack a cell wall, in the class Mollicutes. ''M. pneumoniae'' is a human pathogen that causes the disease Mycoplasma pneumonia, a form of atypical bacterial pneumonia related ...

''. Additionally, doxycycline is used in the prevention and treatment of serious conditions like anthrax, leptospirosis, bubonic plague, and Lyme disease. However, some bacteria, including ''

Haemophilus ''Haemophilus'' is a genus of Gram-negative, pleomorphic, coccobacilli bacteria belonging to the family Pasteurellaceae. While ''Haemophilus'' bacteria are typically small coccobacilli, they are categorized as pleomorphic bacteria because of ...

'' spp., ''

Mycoplasma hominis ''Mycoplasma hominis'' (also known as ''Metamycoplasma hominis'') is a species of bacteria in the genus '' Mycoplasma''. ''M.hominis'' has the ability to penetrate the interior of human cells. Along with ureaplasmas, mycoplasmas are the smallest ...

'', and ''

Pseudomonas aeruginosa ''Pseudomonas aeruginosa'' is a common Bacterial capsule, encapsulated, Gram-negative bacteria, Gram-negative, Aerobic organism, aerobic–facultative anaerobe, facultatively anaerobic, Bacillus (shape), rod-shaped bacteria, bacterium that can c ...

'', have shown resistance to doxycycline. It is also effective against ''

Yersinia pestis ''Yersinia pestis'' (''Y. pestis''; formerly ''Pasteurella pestis'') is a Gram-negative bacteria, gram-negative, non-motile bacteria, non-motile, coccobacillus Bacteria, bacterium without Endospore, spores. It is related to pathogens ''Yer ...

'' (the infectious agent of

bubonic plague Bubonic plague is one of three types of Plague (disease), plague caused by the Bacteria, bacterium ''Yersinia pestis''. One to seven days after exposure to the bacteria, flu-like symptoms develop. These symptoms include fever, headaches, and ...

), and is prescribed for the treatment of

ehrlichiosis Ehrlichiosis is a tick-borne bacterial infection, caused by bacteria of the family Anaplasmataceae, genera '' Ehrlichia'' and '' Anaplasma''. These obligate intracellular bacteria infect and kill white blood cells. The average reported annua ...

, and

Rocky Mountain spotted fever Rocky Mountain spotted fever (RMSF) is a bacterial disease spread by ticks. It typically begins with a fever and headache, which is followed a few days later with the development of a rash. The rash is generally Petechial rash, made up of small s ...

. Specifically, doxycycline is indicated for treatment of the following diseases: *

fever and the typhus group,

scrub typhus Scrub typhus or bush typhus is a form of typhus caused by the intracellular parasite '' Orientia tsutsugamushi'', a Gram-negative α-proteobacterium of family Rickettsiaceae first isolated and identified in 1930 in Japan.

Q fever Q fever or query fever is a disease caused by infection with ''Coxiella burnetii'', a bacterium that affects humans and other animals. This organism is uncommon, but may be found in cattle, sheep, goats, and other domestic mammals, including ...

rickettsialpox Rickettsialpox is a mite-borne infectious illness caused by bacteria of the genus '' Rickettsia'' ('' Rickettsia akari''). Physician Robert Huebner and self-trained entomologist Charles Pomerantz played major roles in identifying the cause of ...

, and tick fevers caused by ''

Rickettsia ''Rickettsia'' is a genus of nonmotile, gram-negative, nonspore-forming, highly pleomorphic bacteria that may occur in the forms of cocci (0.1 μm in diameter), bacilli (1–4 μm long), or threads (up to about 10 μm long). The genus was n ...

'', * respiratory tract infections caused by ''

'', *

Lymphogranuloma venereum Lymphogranuloma venereum (LGV; also known as climatic bubo, Durand–Nicolas–Favre disease, poradenitis inguinale, lymphogranuloma inguinale, and strumous bubo) is a sexually transmitted infection caused by the invasive serovars L1, L2, L2a, ...

trachoma Trachoma is an infectious disease caused by bacterium '' Chlamydia trachomatis''. The infection causes a roughening of the inner surface of the eyelids. This roughening can lead to pain in the eyes, breakdown of the outer surface or cornea ...

inclusion conjunctivitis Conjunctivitis, also known as pink eye or Madras eye, is inflammation of the conjunctiva, the thin, clear layer that covers the white surface of the eye and the inner eyelid. It makes the eye appear pink or reddish. Pain, burning, scratchiness ...

, and uncomplicated urethral, endocervical, or rectal infections in adults caused by ''

Chlamydia trachomatis ''Chlamydia trachomatis'' () is a Gram-negative, Anaerobic organism, anaerobic bacterium responsible for Chlamydia infection, chlamydia and trachoma. ''C. trachomatis'' exists in two forms, an extracellular infectious elementary body (EB) and an ...

'', *

psittacosis Psittacosis—also known as parrot fever, and ornithosis—is a zoonotic infectious disease in humans caused by a bacterium called '' Chlamydia psittaci'' and contracted from infected parrots, such as macaws, cockatiels, and budgerigars, and ...

, *

caused by ''

Ureaplasma urealyticum ''Ureaplasma urealyticum'' is a bacterium belonging to the genus '' Ureaplasma'' and the family Mycoplasmataceae in the order Mycoplasmatales. This family consists of the genera ''Mycoplasma'' and '' Ureaplasma''. Its type strain is T960. The ...

'', * relapsing fever due to ''Borrelia recurrentis'', * chancroid caused by ''Haemophilus ducreyi'', * plague due to ''

'', * tularemia, *

, * ''campylobacter fetus'' infections, * brucellosis caused by ''Brucella'' species (in conjunction with streptomycin), * bartonellosis, * granuloma inguinale (''Klebsiella'' species), *

(''Borrelia'' species).

Gram-negative bacteria specific indications

When bacteriologic testing indicates appropriate susceptibility to the drug, doxycycline may be used to treat these infections caused by Gram-negative bacteria: * ''Escherichia coli'' infections, * ''Enterobacter aerogenes'' (formerly ''Aerobacter aerogenes'') infections, * ''Shigella'' species infections, * ''Acinetobacter'' species (formerly ''Mima'' species and ''Herellea'' species) infections, * respiratory tract infections caused by ''Haemophilus influenzae'', * respiratory tract and urinary tract infections caused by ''Klebsiella'' species.

Gram-positive bacteria specific indications

Some Gram-positive bacteria have developed resistance to doxycycline. Up to 44% of ''Streptococcus pyogenes'' and up to 74% of ''Streptococcus faecalis, S. faecalis'' specimens have developed resistance to the Tetracycline antibiotics, tetracycline group of antibiotics. Up to 57% of Cutibacterium acnes, ''P. acnes'' strains developed resistance to doxycycline. When bacteriologic testing indicates appropriate susceptibility to the drug, doxycycline may be used to treat these infections caused by Gram-positive bacteria: * upper respiratory infections caused by ''Streptococcus pneumoniae'' (formerly ''Diplococcus pneumoniae''), * skin and soft tissue infections caused by ''Staphylococcus aureus'', including methicillin-resistant Staphylococcus aureus, methicillin-resistant ''Staphylococcus aureus'' infections, * anthrax caused by ''Bacillus anthracis'' infection.

Specific applications of doxycycline when penicillin is contraindicated

When penicillin is contraindicated, doxycycline can be used to treat: *

caused by ''Treponema pallidum'', * yaws caused by ''Treponema pertenue'', * listeriosis due to ''Listeria monocytogenes'', * Vincent's infection caused by ''Fusobacterium fusiforme'', * actinomycosis caused by ''Actinomyces israelii'', * infections caused by ''Clostridium'' species.

Use as adjunctive therapy

Doxycycline may also be used as adjunctive therapy for severe acne. Subantimicrobial-dose doxycycline (SDD) is widely used as an adjunctive treatment to scaling and root planing for periodontitis. Significant differences were observed for all investigated clinical parameters of periodontitis in favor of the scaling and root planing + SDD group where SDD dosage regimens is 20 mg twice daily for three months in a meta-analysis published in 2011. SDD is also used to treat skin conditions such as acne and rosacea, 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. Doxycycline is used as an adjunctive therapy for acute intestinal amebiasis. Doxycycline is also used as an adjunctive therapy for chancroid.

As prophylaxis against sexually transmitted infections

Doxycycline is used for post-exposure prophylaxis (PEP) to reduce the incidence of sexually transmitted bacterial infections (STIs), but it has been associated with tetracycline resistance in associated species, in particular, in Neisseria gonorrhoeae. For this reason, the Australian consensus statement mentions that doxycycline for PEP particularly in gay, bisexual, and other men who have sex with men (GBMSM) should be considered only for the prevention of syphilis in GBMSM, and that the risk of increasing antimicrobial resistance outweighed any potential benefit from reductions in other bacterial STIs in GBMSM. Appropriate use of doxycycline for PEP is supported by guidelines from the Centers for Disease Control and Prevention, US Centers for Disease Control and Prevention (CDC) and the Australasian Society for HIV Medicine.

Use in combination

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

Antimalarial

Doxycycline is active against the erythrocytic stages of ''Plasmodium falciparum'' but not against the gametocytes of ''P. falciparum''. It is used to prevent

. It is not recommended alone for initial treatment of malaria, even when the parasite is doxycycline-sensitive, because the antimalarial effect of doxycycline is delayed. Doxycycline blocks protein production in

(an organelle) of ''P. falciparum''—such blocking leads to two main effects: it disrupts the parasite's ability to produce fatty acids, which are essential for its growth, and it impairs the production of heme, a cofactor. These effects occur late in the parasite's life cycle when it is in the blood stage, causing the symptoms of malaria. By blocking important processes in the parasite, doxycycline both inhibits the growth and prevents the multiplication of ''P. falciparum''. It does not directly kill the living organisms of ''P. falciparum'' but creates conditions that prevent their growth and replication. 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 ''Plasmodium falciparum, P. falciparum'' or following intravenous treatment of severe malaria.

Antihelminthic

Doxycycline kills the symbiosis, symbiotic ''Wolbachia'' bacteria in the reproductive tracts of parasitic filarial nematodes, making the nematodes sterile, and thus reducing transmission of diseases such as onchocerciasis and elephantiasis tropica, elephantiasis. Field trials in 2005 showed an eight-week course of doxycycline almost eliminates the release of microfilariae.

Spectrum of susceptibility

Doxycycline has been used successfully to treat sexually transmitted, respiratory, and ophthalmic infections. Representative pathogenic genera include ''Chlamydia, Streptococcus, Ureaplasma, Mycoplasma'', and others. The following represents minimum inhibitory concentration susceptibility data for a few medically significant microorganisms. * ''Chlamydia psittaci'': 0.03 ''μ''g/mL * ''

'': 0.016–2 ''μ''g/mL * ''Streptococcus pneumoniae'': 0.06–32 ''μ''g/mL

Sclerotherapy

Doxycycline is also used for sclerotherapy in slow-flow vascular malformations, namely Venous malformation, venous and lymphatic malformations, as well as post-operative lymphoceles.

Off-label use

Doxycycline has found off-label use in the treatment of transthyretin amyloidosis (ATTR). Together with tauroursodeoxycholic acid, doxycycline appears to be a promising combination capable of disrupting transthyretin TTR fibrils in existing amyloid deposits of ATTR patients.

Routes of administration

Doxycycline can be administered via oral or intravenous routes. The combination of doxycycline with dairy, antacids, calcium supplements, iron products, laxatives containing magnesium, or bile acid sequestrants is not inherently dangerous, but any of these foods and supplements may decrease absorption of doxycycline. Doxycycline has a high oral bioavailability, as it is almost completely absorbed in the stomach and proximal small intestine. Unlike other tetracyclines, its absorption is not significantly affected by food or dairy intake. However, co-administration of dairy products reduces the serum concentration of doxycycline by 20%. Doxycycline absorption is also inhibited by divalent and trivalent cations, such as iron, bismuth, aluminum, calcium and magnesium. Doxycycline forms unstable complexes with metal ions in the acidic gastric environment, which 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.

Contraindications

Severe liver disease or concomitant use of isotretinoin or other retinoids are contraindications, as both tetracyclines and retinoids can cause intracranial hypertension (increased pressure around the brain) in rare cases.

Pregnancy and lactation

Doxycycline is categorized by the Food and Drug Administration, FDA as a Pregnancy category#United States, class D drug in pregnancy. Doxycycline crosses into breastmilk. Other tetracycline antibiotics are contraindicated in pregnancy and up to eight years of age, due to the potential for disrupting bone and tooth development. They include a class warning about staining of teeth and decreased development of dental enamel in children exposed to tetracyclines in utero, during breastfeeding or during young childhood. 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 of dental enamel or on staining of teeth. The Centers for Disease Control and Prevention, CDC recommends the use of doxycycline for treatment of

and tick-borne Rickettsial disease, rickettsial diseases in young children; others advocate for its use in malaria.

Adverse effects

Adverse effects are similar to those of other members of the Tetracycline antibiotics, tetracycline antibiotic group. Doxycycline can cause gastrointestinal upset. Oral doxycycline can cause pill esophagitis, particularly when it is swallowed without adequate fluid, or by persons with difficulty swallowing or impaired mobility. Doxycycline is less likely than other antibiotic drugs to cause ''Clostridioides difficile infection, Clostridioides difficile'' colitis''.'' An erythematous 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. One study examined the tolerability of various malaria prophylactic regimens and found doxycycline did not cause a significantly higher percentage of all skin events (photosensitivity not specified) when compared with other antimalarials. The rash resolves upon discontinuation of the drug. Unlike some other members of the tetracycline group, it may be used in those with renal impairment. Doxycycline use has been associated with increased risk of inflammatory bowel disease. In one large Retrospective cohort study, retrospective study, patients who were prescribed doxycycline for their acne had a 2.25-fold greater risk of developing Crohn's disease.

Interactions

Previously, doxycycline was believed to impair the effectiveness of many types of hormonal contraception due to Cytochrome P450, CYP450 induction. 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.

Pharmacology

Doxycycline, like other tetracycline antibiotics, is Bacteriostatic agent, bacteriostatic. It works by preventing bacteria from reproducing by inhibiting Protein biosynthesis, protein synthesis. Doxycycline is highly Lipophilicity, lipophilic, so it can easily enter cells, meaning the drug is easily absorbed after oral administration and has a large volume of distribution. It can also be re-absorbed in the renal tubules and gastrointestinal tract due to its high lipophilicity, giving it a long Biological half-life, elimination half-life. It is also prevented from accumulating in the kidneys of patients with kidney failure due to the compensatory excretion in Feces, faeces. Doxycycline–metal ion complexes are unstable at acidic pH, therefore more doxycycline enters the duodenum for absorption than the earlier tetracycline compounds. In addition, food has less effect on the absorption of doxycycline than on the absorption of earlier drugs, with doxycycline serum concentrations being reduced by about 20% by test meals compared with 50% for tetracycline.

Mechanism of action

Doxycycline is a broad-spectrum bacteriostatic agent, bacteriostatic antibiotic. It inhibits the synthesis of bacterial proteins by binding to the 30S ribosomal subunit, which is only found in bacteria. This prevents the binding of transfer RNA to messenger RNA at the ribosomal subunit, meaning Amino acid, amino acids cannot be added to Peptide, polypeptide chains and new proteins cannot be made. This stops bacterial growth, giving the immune system time to kill and remove the bacteria. In rosacea treatment, doxycycline inhibits neutrophil chemotaxis and Oxidative burst, oxidative bursts (common mechanisms of inflammation and reactive oxygen species activity in rosacea), and it also suppresses Matrix metalloproteinase, matrix metalloproteases and Kallikrein-5, kallikrein 5 which in turn reduce the expression of the LL-37, human cathelicidin antimicrobial peptide (LL-37) and limit downstream inflammatory cascades.

Pharmacokinetics

The substance is almost completely absorbed from the upper part of the small intestine. 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 Tissue (biology), 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.Doxycycline . Accessed 5 August 2020. By comparison, the tetracycline antibiotic minocycline penetrates significantly better into the CSF and meninges. Doxycycline metabolism is negligible. It is actively excreted into the gut (in part via the gallbladder, in part directly from Blood vessel, 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) in healthy people, slightly longer in those with end-stage kidney disease, and significantly longer in those with liver disease.

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 causing Fanconi syndrome. In the case of doxycycline, the absence of a hydroxyl group in C-6 prevents the formation of the nephrotoxic compound. 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.

Chemical properties

Doxycycline, doxycycline Water of crystallization, 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

[\alpha]_D^

−110° cm³/dm·g in 0.01 Normality (chemistry), N methanolic hydrochloric acid.

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 antibiotic, tetracycline class of antibiotics. 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 FDA in 1967. As its patent grew near to expiring in the early 1970s, the patent became the subject of lawsuit between Pfizer and International Rectifier that was not resolved until 1983; at the time it was the largest litigated patent case in US history. Instead of a cash payment for infringement, Pfizer took the veterinary and feed-additive businesses of International Rectifier's subsidiary, Rachelle Laboratories. In January 2013, the FDA reported shortages of some, but not all, forms of doxycycline "caused by increased demand and manufacturing issues". Companies involved included an unnamed major generics manufacturer that ceased production in February 2013, Teva Pharmaceutical Industries, Teva (which ceased production in May 2013), Mylan, Actavis, and Hikma Pharmaceuticals. The shortage came at a particularly bad time, since there were also shortages of an alternative antibiotic, tetracycline, at the same time. 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), before decreasing again.

Society and culture

Doxycycline is available worldwide under many brand names. Doxycycline is available as a generic medicine. Doxycycline is also used in the prevention of certain sexually transmitted infections, particularly among men who have sex with men.

Research

Medical conditions

Research areas on the application of doxycycline include the following medical conditions: * macular degeneration; * rheumatoid arthritis instead of minocycline (both of which have demonstrated modest efficacy for this disease). Tet-ON inducible transgene expression cells

Tet-ON inducible transgene expression cells

Dosing

Although doxycycline is approved to treat

, the optimal dosing and duration of treatment for this condition is a topic of ongoing research. 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. 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.

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) 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, 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. A potential explanation of doxycycline's anti-inflammatory properties is its inhibition of matrix metalloproteinases (MMPs), 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. Doxycycline has been shown to inhibit MMPs, including MMP7, matrilysin (MMP7), by interacting with the structural zinc atom and/or calcium atoms within the structural metal center of the protein. Doxycycline also inhibits allikrein-related peptidase 5 (KLK5). 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. Doxycycline is used to treat Acne, acne vulgaris and

. However, there is no clear understanding of what contributes more: the bacteriostatic properties of doxycycline, which affect bacteria (such as Propionibacterium acnes) on the surface of sebaceous glands even in lower doses called "submicrobial" or "subantimicrobial", or whether doxycycline's anti-inflammatory effects, which reduce inflammation in Acne, acne vulgaris and

, including ocular rosacea, contribute more to its therapeutic effectiveness against these skin conditions. Subantimicrobial-dose doxycycline (SDD) can still have a Bacteriostatic agent, bacteriostatic effect, especially when taken for extended periods, such as several months in treating acne and rosacea. 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. 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 Reactive oxygen species, 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. Studies have shown that SDD can effectively improve acne and rosacea symptoms, probably without inducing Antimicrobial resistance, antibiotic resistance. 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. 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 Periodontal disease, periodontitis. 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. Doxycycline has been studied in various immunological disorders, including rheumatoid arthritis, lupus, and Periodontal disease, periodontitis. 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. Doxycycline is also studied for its neuroprotective properties which are associated with antioxidant, Apoptosis, 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 Synapse, synaptic proteins. 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. It has been demonstrated that doxycycline mimics nerve growth factor (NGF) signaling in PC12 cell line, 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 Major depressive disorder, depression. While there is some research on the use of doxycycline for treating major depressive disorder, the results are mixed. After a large-scale trial showed no benefit of using doxycycline in treating COVID-19, COVID19, the UK's National Institute for Health and Care Excellence (NICE) updated its guidance to not recommend the medication for the treatment of COVID19. 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. 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.

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. 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.

Research reagent

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. 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. Doxycycline is more stable than tetracycline for this purpose. At subantimicrobial doses, doxycycline is an inhibitor of matrix metalloproteases, and has been used in various experimental systems for this purpose, such as for recalcitrant recurrent corneal erosions.

References

External links

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