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Current Molecular Pharmacology 2021Minocycline and doxycycline both are second-generation tetracycline antibiotics with similar chemical structures and comparable antibacterial spectrum. Minocycline has... (Review)
Review
Minocycline and doxycycline both are second-generation tetracycline antibiotics with similar chemical structures and comparable antibacterial spectrum. Minocycline has also emerged as the tetracycline of choice for multidrug-resistant Acinetobacter baumannii infections, although doxycycline has also shown the activity. Minocycline showed promising results in experimental neurology, which was due to its highly lipophilic nature. It is clinically safe and effective adjunct to antipsychotic medications. The objective of the current review is to provide clinical and preclinical, non-antibiotic uses of minocycline as well as doxycycline. Relevant literature covers antibiotic actions but is more specifically concerned with the non-antibiotic biological aspect of tetracyclines. Non-antibiotic biological effects for both the antibiotics were identified through searching relevant databases including: PubMed, Scopus, and Web of Science up to 2020, using the keywords 'minocycline and doxycycline'. Anti-inflammatory, anti-oxidant, anti-apoptotic neuroprotective, immunomodulatory and the number of other non-antibiotic effects were compiled for minocycline and doxycycline.
Topics: Anti-Bacterial Agents; Doxycycline; Minocycline; Tetracycline
PubMed: 33568043
DOI: 10.2174/1874467214666210210122628 -
The New England Journal of Medicine Dec 2023Doxycycline postexposure prophylaxis (PEP) has been shown to prevent sexually transmitted infections (STIs) among cisgender men and transgender women, but data from... (Comparative Study)
Comparative Study Randomized Controlled Trial
BACKGROUND
Doxycycline postexposure prophylaxis (PEP) has been shown to prevent sexually transmitted infections (STIs) among cisgender men and transgender women, but data from trials involving cisgender women are lacking.
METHODS
We conducted a randomized, open-label trial comparing doxycycline PEP (doxycycline hyclate, 200 mg taken within 72 hours after condomless sex) with standard care among Kenyan women 18 to 30 years of age who were receiving preexposure prophylaxis against human immunodeficiency virus (HIV). The primary end point was any incident infection with , , or . Hair samples were collected quarterly for objective assessment of doxycycline use.
RESULTS
A total of 449 participants underwent randomization; 224 were assigned to the doxycycline-PEP group and 225 to the standard-care group. Participants were followed quarterly over 12 months. A total of 109 incident STIs occurred (50 in the doxycycline-PEP group [25.1 per 100 person-years] and 59 in the standard-care group [29.0 per 100 person-years]), with no significant between-group difference in incidence (relative risk, 0.88; 95% confidence interval [CI], 0.60 to 1.29; P = 0.51). Among the 109 incident STIs, chlamydia accounted for 85 (78.0%) (35 in the doxycycline-PEP group and 50 in the standard-care group; relative risk, 0.73; 95% CI, 0.47 to 1.13). No serious adverse events were considered by the trial investigators to be related to doxycycline, and there were no incident HIV infections. Among 50 randomly selected participants in the doxycycline-PEP group, doxycycline was detected in 58 of 200 hair samples (29.0%). All -positive isolates were resistant to doxycycline.
CONCLUSIONS
Among cisgender women, the incidence of STIs was not significantly lower with doxycycline PEP than with standard care. According to hair-sample analysis, the use of doxycycline PEP among those assigned to receive it was low. (Funded by the National Institutes of Health; dPEP ClinicalTrials.gov number, NCT04050540.).
Topics: Female; Humans; Chlamydia Infections; Chlamydia trachomatis; Doxycycline; HIV Infections; Kenya; Neisseria gonorrhoeae; Pre-Exposure Prophylaxis; Sexually Transmitted Diseases; Unsafe Sex; Anti-Infective Agents; Adolescent; Young Adult; Adult; Gonorrhea; Treponema pallidum; Syphilis; Drug Monitoring; Hair
PubMed: 38118022
DOI: 10.1056/NEJMoa2304007 -
Biomedical Journal Dec 2022We investigated the relationship between inducible nitric oxide synthase (iNOS) and arginase pathways, cytokines, macrophages, oxidative damage and lung granulomatous...
BACKGROUND
We investigated the relationship between inducible nitric oxide synthase (iNOS) and arginase pathways, cytokines, macrophages, oxidative damage and lung granulomatous inflammation in S. mansoni-infected and doxycycline-treated mice.
METHODS
Swiss mice were randomized in four groups: (i) uninfected, (ii) infected with S. mansoni, (iii) infected + 200 mg/kg praziquantel (Pzt), (iv) and (v) infected + 5 and 50 mg/kg doxycycline. Pzt (reference drug) was administered in a single dose and doxycycline for 60 days.
RESULTS
S. mansoni-infection determined extensive lung inflammation, marked recruitment of M2 macrophages, cytokines (IL-4, IL-5, IFN-γ, TNF-α) upregulation, intense eosinophil peroxidase (EPO) levels, arginase expression and activity, reduced iNOS expression and nitric oxide (NO) production. The higher dose of doxycycline aggravated lung granulomatous inflammation, downregulating IL-4 levels and M2 macrophages recruitment, and upregulating iNOS expression, EPO, NO, IFN-γ, TNF-α, M1 macrophages, protein carbonyl and malondialdehyde tissue levels. The number and size of granulomas in doxycycline-treated animals was higher than untreated and Pzt-treated mice. Exudative/productive granulomas were predominant in untreated and doxycycline-treated animals, while fibrotic/involutive granulomas were more frequent in Pzt-treated mice. The reference treatment with Pzt attenuated all these parameters.
CONCLUSION
Our findings indicated that doxycycline aggravated lung granulomatous inflammation in a dose-dependent way. Although Th1 effectors are protective against several intracellular pathogens, effective schistosomicidal responses are dependent of the Th2 phenotype. Thus, doxycycline contributes to the worsening of lung granulomatous inflammation by potentiating eosinophils influx and downregulating Th2 effectors, reinforcing lipid and protein oxidative damage in chronic S. mansoni infection.
Topics: Mice; Animals; Nitric Oxide Synthase Type II; Doxycycline; Arginase; Tumor Necrosis Factor-alpha; Interleukin-4; Schistosomiasis; Cytokines; Lung; Oxidative Stress; Inflammation; Granuloma; Nitric Oxide
PubMed: 34971826
DOI: 10.1016/j.bj.2021.12.007 -
Journal of Pharmaceutical Sciences Apr 2010Literature data relevant to the decision to allow a waiver of in vivo bioequivalence (BE) testing for the approval of immediate release (IR) solid oral dosage forms... (Review)
Review
Literature data relevant to the decision to allow a waiver of in vivo bioequivalence (BE) testing for the approval of immediate release (IR) solid oral dosage forms containing doxycycline hyclate are reviewed. According to the Biopharmaceutics Classification System (BCS), doxycycline hyclate can be assigned to BCS Class I. No problems with BE of IR doxycycline formulations containing different excipients and produced by different manufacturing methods have been reported and hence the risk of bioinequivalence caused by these factors appears to be low. Doxycycline has a wide therapeutic index. Further, BCS-based dissolution methods have been shown to be capable of identifying formulations which may dissolve too slowly to generate therapeutic levels. It is concluded that a biowaiver is appropriate for IR solid oral dosage forms containing doxycycline hyclate as the single Active Pharmaceutical Ingredient (API) provided that (a) the test product contains only excipients present in doxycycline hyclate IR solid oral drug products approved in the International Conference on Harmonization (ICH) or associated countries; and (b) the comparator and the test products comply with the BCS criteria for "very rapidly dissolving" or, alternatively, when similarity of the dissolution profiles can be demonstrated and the two products are "rapidly dissolving.".
Topics: Anti-Bacterial Agents; Dosage Forms; Doxycycline; Drug Approval; Humans; Solubility; Therapeutic Equivalency
PubMed: 19798752
DOI: 10.1002/jps.21954 -
Therapeutic Drug Monitoring 1982The chemistry, mode of action, antimicrobial activity, pharmacokinetics, and therapeutic efficacy of doxycycline are reviewed. Doxycycline displays excellent activity... (Review)
Review
The chemistry, mode of action, antimicrobial activity, pharmacokinetics, and therapeutic efficacy of doxycycline are reviewed. Doxycycline displays excellent activity against gram-positive and gram-negative aerobic and anaerobic pathogens. The oral absorption of doxycycline is rapid and virtually complete and is not significantly decreased by food. Moreover, serum concentrations of doxycycline following oral and intravenous (i.v.) administration are comparable. Because of the prolonged half-life of doxycycline, once daily administration is possible. Tissue penetration of doxycycline is excellent. Levels within the therapeutic range have been found in most organs and tissues, including kidney, lung, gallbladder, prostate, intestinal tract, myocardium, sinus secretions, tonsil, aqueous humor, and female reproductive tissue. Doxycycline does not accumulate in patients with renal insufficiency and is not removed from the blood to any great extent during hemodialysis. Extensive clinical investigation has shown doxycycline to be highly effective in infections of the respiratory tract, including atypical pneumonias; skin and soft tissue; genitourinary infection including gonorrhea, syphilis, nonspecific urethritis, and prostatitis; intraabdominal infection due to trauma, sepsis, or surgery; and cholera. Evidence also suggests that doxycycline will prove effective in the treatment of Legionnaires' disease. In addition, placebo-controlled clinical trials suggest doxycycline is effective in the prevention of traveler's diarrhea.
Topics: Abdomen; Animals; Bacteria; Bacterial Infections; Chemical Phenomena; Chemistry; Clinical Laboratory Techniques; Doxycycline; Drug Interactions; Female; Genital Diseases, Female; Genital Diseases, Male; Humans; Intestinal Absorption; Kinetics; Male; Respiratory Tract Infections; Skin Diseases, Infectious; Tissue Distribution; Urinary Tract Infections
PubMed: 7048645
DOI: 10.1097/00007691-198206000-00001 -
Oxidative Medicine and Cellular... 2021The main objective of this study was to investigate the action of doxycycline hyclate (Dx) in the skin wound healing process in Wistar rats. We investigated the effect...
The main objective of this study was to investigate the action of doxycycline hyclate (Dx) in the skin wound healing process in Wistar rats. We investigated the effect of Dx on inflammatory cell recruitment and production of inflammatory mediators via and analysis. In addition, we analyzed neovascularization, extracellular matrix deposition, and antioxidant potential of Dx on cutaneous repair in Wistar rats. Male animals ( = 15) were divided into three groups with five animals each (protocol: 72/2017), and three skin wounds (12 mm diameter) were created on the back of the animals. The groups were as follows: C, received distilled water (control); Dx1, doxycycline hyclate (10 mg/kg/day); and Dx2, doxycycline hyclate (30 mg/kg/day). The applications were carried out daily for up to 21 days, and tissues from different wounds were removed every 7 days. Our analysis demonstrated that Dx led to macrophage proliferation and increased N-acetyl--D-glucosaminidase (NAG) production, besides decreased cyclooxygenase-2 (COX-2), prostaglandin E2 (PGE2), and metalloproteinases (MMP), which indicates that macrophage activation and COX-2 inhibition are possibly regulated by independent mechanisms. , our findings presented increased cellularity, blood vessels, and the number of mast cells. However, downregulation was observed in the COX-2 and PGE2 expression, which was limited to epidermal cells. Our results also showed that the downregulation of this pathway benefits the oxidative balance by reducing protein carbonyls, malondialdehyde, nitric oxide, and hydrogen peroxide (HO). In addition, there was an increase in the antioxidant enzymes (catalase and superoxide dismutase) after Dx exposure, which demonstrates its antioxidant potential. Finally, Dx increased the number of types I collagen and elastic fibers and reduced the levels of MMP, thus accelerating the closure of skin wounds. Our findings indicated that both doses of Dx can modulate the skin repair process, but the best effects were observed after exposure to the highest dose.
Topics: Animals; Male; Rats; Anti-Bacterial Agents; Antioxidants; Cyclooxygenase 2; Doxycycline; Matrix Metalloproteinases; Rats, Wistar; Wound Healing
PubMed: 33959214
DOI: 10.1155/2021/4681041 -
Pharmaceutical Nanotechnology 2022Acne is the pilosebaceous units' disorder. The most important cause of acne is the colonization of bacteria in the follicles. Among antibiotics, doxycycline hyclate...
BACKGROUND
Acne is the pilosebaceous units' disorder. The most important cause of acne is the colonization of bacteria in the follicles. Among antibiotics, doxycycline hyclate kills a wide range of bacteria.
OBJECTIVES
The study aims to prevent oral administration's side effects, overcome the barriers of conventional topical treatment, and improve the therapeutic effectiveness; this drug was loaded into niosomal nanocarriers for topical application.
METHODS
Doxycycline hyclate was loaded into four niosomal formulations prepared by the thinfilm hydration method with different percentages of constituents. Drug-containing niosomal systems were evaluated for morphological properties via scanning electron microscopy, particle size, drug entrapment efficiency, zeta potential, in vitro drug release, physical stability after 60 days, in vitro drug permeation through rat skin, in vitro drug deposition in rat skin, toxicity on human dermal fibroblasts (HDF) by MTT method after 72 hours, and antibacterial properties against the main acne-causing bacteria via antibiogram test.
RESULTS
The best formulation had the appropriate particle size of 362.88 ± 13.05 nm to target follicles, entrapment efficiency of 56.3 ± 2.1%, the zeta potential of - 24.46±1.39 mV, in vitro drug release of 54.93 ± 1.99% after 32 hours, and the lowest permeation of the drug through the rat skin among all other formulations. Improved cell viability, increased antibacterial activity, and an approximately three-fold increase in drug deposition were the optimal niosomal formulation features relative to the free drug.
CONCLUSION
This study demonstrated the ability of nano-niosomes containing doxycycline hyclate to treat skin acne compared with the free drug.
Topics: Acne Vulgaris; Animals; Anti-Bacterial Agents; Doxycycline; Drug Delivery Systems; Liposomes; Rats
PubMed: 35209832
DOI: 10.2174/2211738510666220224103406 -
Expert Opinion on Drug Safety Sep 2008Tetracyclines have long been used to treat a wide variety of medical conditions, especially in the field of dermatology. Unfortunately, safety concerns, especially... (Review)
Review
Tetracyclines have long been used to treat a wide variety of medical conditions, especially in the field of dermatology. Unfortunately, safety concerns, especially gastrointestinal (GI), have always been present. Other safety concerns have included tooth development in children, candidiasis, vestibular concerns, photosensitivity/phototoxicity, and more unusual adverse effects such as uncontrolled hypertension. This article first discusses the pharmacological development of the tetracyclines from the first to the second generation versions with an emphasis on the safety concerns, especially with regards to doxycycline hyclate (DH). Second, the adverse effects of the tetracyclines are discussed. Third, the favorable side effect profile of DH delayed release capsules (Doryx) is compared with DH powder contained in tablets (Vibramycin). Fourth, the increased use with a continued favorable safety profile is also discussed concerning the subantimicrobial dosing of DH for acne. Fifth, the safety of periodontic uses of DH is discussed. Last, the favorable safety profiles of the 2006 approved uses of an anti-inflammatory dose of 40 mg doxycycline for rosacea and an extended-release minocycline tablet for acne are also discussed.
Topics: Anti-Bacterial Agents; Child; Dosage Forms; Dose-Response Relationship, Drug; Doxycycline; Humans; Periodontal Diseases; Tetracyclines
PubMed: 18759709
DOI: 10.1517/14740338.7.5.571 -
European Journal of Pharmaceutical... Jan 2020Doxycycline hiclate is a broad spectrum antibiotic widely used in human and veterinary medicine. The inability to perform the parenteral administration of drugs and the...
Doxycycline hiclate is a broad spectrum antibiotic widely used in human and veterinary medicine. The inability to perform the parenteral administration of drugs and the lack of oral preparations can be mentioned as difficulties in the treatment of animals in the domestic environment. In this scenario, the aim of this study was to investigate the bioavailability of the drug by rectal route, to propose a potential suppository formulation containing 25 mg of doxycycline as an alternative to the available injectable formulations. Hydrophilic and lipophilic suppositories were prepared, in polyethylene glycol (S-PEG) or cocoa butter (S-CBT), respectively. The suppositories were prepared and evaluated concerning visual characteristics, content, average weight, melting range, content uniformity and in vitro release. A stability study was performed and the two most stable formulations were submitted to a pharmacokinetic study in rabbits. The bioavailability of the suppositories was compared to the data of the intravenous (i.v.) formulation. PEG suppository showed 49.13% bioavailability and CBT 51.43% with C equal to 2.06 ± 2.96 µg.mL and 1.54 ± 0.28 µg.mL, respectively. The data obtained suggest that rectal administration may become another method of administration of doxycycline in the treatment of bacterial infections.
Topics: Administration, Rectal; Animals; Anti-Bacterial Agents; Bacterial Infections; Biological Availability; Chemistry, Pharmaceutical; Doxycycline; Male; Polyethylene Glycols; Rabbits
PubMed: 31706017
DOI: 10.1016/j.ejps.2019.105141 -
AAPS PharmSciTech Feb 2021Currently, periodontitis is treated by oral dosage forms (antibiotics) which shows systemic side effects and failed to reach the therapeutic concentration (above minimum...
Currently, periodontitis is treated by oral dosage forms (antibiotics) which shows systemic side effects and failed to reach the therapeutic concentration (above minimum inhibitory concentration, MIC) in the periodontal pocket. The present study aimed to overcome the above issues, by designing tailored doxycycline hyclate laden in situ gel by Poloxamer 407, chitosan, and polyethylene glycol 600. The in situ gel-forming system has attracted attention owing to its ability of sustained drug release above MIC, easy administration (syringeability), and high drug retention (localization) in the periodontal cavity. The Box-Behnken design (BBD) was used to tailor and optimize the concentration of Poloxamer 407 (X = 14.3%), chitosan (X = 0.58%), and polyethylene glycol 600 (X = 1.14%) to achieve sufficient syringeability (149 N), t (1105 min), and viscosity at non-physiological condition (512 cps) and physiological condition (5415 cps). The optimized in situ gel was clear and isotonic (RBCs test). The gelation temperature of the optimized in situ was 34 ± 1°C with sufficient mucoadhesive strength (26 ± 2 dyn/cm), gel strength (29 ± 2 sec), and texture profile for periodontal application. The in vitro drug release studies showed sustain release from optimized in situ gel (24h) in comparison to marketed gel (7h). The antimicrobial activity (cup plate technique) of the in situ gel was equivalent to the marketed doxycycline gel, which suggests that the doxycycline hyclate retained its antimicrobial efficacy when formulated as in situ gelling system. In conclusion, BBD was effectively utilized to optimize in situ gel with minimum level of polymers to achieve the required characteristics of the in situ gel for sustaining drug delivery to treat periodontitis.
Topics: Anti-Bacterial Agents; Chitosan; Doxycycline; Drug Delivery Systems; Drug Liberation; Gels; Humans; Periodontitis; Poloxamer; Polymers
PubMed: 33595740
DOI: 10.1208/s12249-021-01950-x