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Journal of Infection in Developing... Feb 2023Doxycycline is an antibiotic with known gastrointestinal (GI) adverse effects. Esophagitis is the most pronounced among these effects, and might be associated with a...
INTRODUCTION
Doxycycline is an antibiotic with known gastrointestinal (GI) adverse effects. Esophagitis is the most pronounced among these effects, and might be associated with a prolonged duration of therapy. The aim of this study is to evaluate the incidence of esophagitis and other GI side effects in adults who received doxycycline for at least a month.
METHODOLOGY
This retrospective descriptive study included adults who received oral doxycycline for at least one month between 2016 and 2018. The primary outcome was the frequency of esophagitis. The secondary outcomes were frequency of and discontinuation due to GI adverse effects.
RESULTS
A total of 189 subjects were included with a median age of 32 years. The median duration of doxycycline use was 44 days (interquartile range 30-60). Twelve patients (6.3%) reported having GI adverse effects resulting in doxycycline discontinuation in five of them (2.6%), and three patients (1.6%) had esophagitis. The incidence of GI adverse effects was significantly higher in patients who were ≥ 50 years than < 50 years old (8/50 vs. 4/139; p = 0.003) and in those who received a daily dose of 200 mg than 100 mg (12/93 vs. 0/96; p < 0.001).
CONCLUSIONS
GI adverse events, including esophagitis, are not rare with long-term use of oral doxycycline, particularly in older age and a higher dose of 200 mg/day. Future large and randomized studies are needed to compare the efficacy and safety of different doxycycline doses.
Topics: Adult; Humans; Doxycycline; Retrospective Studies; Anti-Bacterial Agents; Esophagitis
PubMed: 36897904
DOI: 10.3855/jidc.16677 -
Indian Journal of Pharmaceutical... Jul 2013To characterize the thermal behavior and texture analysis of doxycycline hyclate thermosensitive gels developed for periodontitis treatment containing zinc oxide...
To characterize the thermal behavior and texture analysis of doxycycline hyclate thermosensitive gels developed for periodontitis treatment containing zinc oxide prepared by using poloxamer (Lutrol(®) F127) as polymeric material and N-methyl pyrrolidone was used as cosolvent. The thermosensitive gel comprising doxycycline hyclate, Lutrol(®) F127, and N-methyl pyrrolidone were characterized for the thermal behavior and texture analysis. The topography of the system after the dissolution test was characterized with scanning electron microscope. Differential scanning calorimetric thermogram exhibited the endothermic peaks in the systems containing high amount of N-methyl pyrrolidone in solvent. The sol-gel transition temperature of the systems decreased as the zinc oxide amount was increased. The addition of doxycycline hyclate, zinc oxide, and N-methyl pyrrolidone affected the syringeability of systems. The addition of zinc oxide into the doxycycline hyclate-Lutrol(®) F127 systems decreased the diameter of inhibition zone against Staphylococcus aureus, Escherichia coli, and Candida albicans since zinc oxide decreased the diffusion and prolonged release of doxycycline hyclate. From scanning electron microscope analysis, the porous surface of 20% w/w Lutrol(®) F127 system was notably different from that of gel comprising doxycycline hyclate which had interconnected pores and smooth surfaces. The number of pores was decreased with increasing zinc oxide and the porous structure was smaller and more compact. Therefore, the addition of zinc oxide could increase the syringeability of doxycycline hyclate-Lutrol(®) F127 system with the temperature dependence. Zinc oxide decreased inhibition zone against test microbes because of prolongation of doxycycline hyclate release and reduced size of continuous cells. Furthermore, zinc oxide also increased the compactness of wall surfaces of Lutrol(®) F127.
PubMed: 24302791
DOI: 10.4103/0250-474x.119807 -
American Journal of Veterinary Research Apr 2015To determine the pharmacokinetics of doxycycline hyclate administered orally in the form of experimental formulations with different proportions of acrylic... (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVE
To determine the pharmacokinetics of doxycycline hyclate administered orally in the form of experimental formulations with different proportions of acrylic acid-polymethacrylate-based matrices.
ANIMALS
30 healthy adult dogs.
PROCEDURES
In a crossover study, dogs were randomly assigned (in groups of 10) to receive a single oral dose (20 mg/kg) of doxycycline hyclate without excipients (control) or extended-release formulations (ERFs) containing doxycycline, acrylic acid polymer, and polymethacrylate in the following proportions: 1:0.5:0.0075 (ERF1) or 1:1:0.015 (ERF2). Serum concentrations of doxycycline were determined for pharmacokinetic analysis before and at several intervals after each treatment.
RESULTS
Following oral administration to the study dogs, each ERF resulted in therapeutic serum doxycycline concentrations for 48 hours, whereas the control treatment resulted in therapeutic serum doxycycline concentrations for only 24 hours. All pharmacokinetic parameters for ERF1 and ERF2 were significantly different; however, findings for ERF1 did not differ significantly from those for the control treatment.
CONCLUSIONS AND CLINICAL RELEVANCE
Results indicated that both ERFs containing doxycycline, acrylic acid polymer, and polymethacrylate had an adequate pharmacokinetic-pharmacodynamic relationship for a time-dependent drug and a longer release time than doxycycline alone following oral administration in dogs. Given the minimum effective serum doxycycline concentration of 0.26 μg/mL, a dose interval of 48 hours can be achieved for each tested ERF. This minimum inhibitory concentration has the potential to be effective against several susceptible bacteria involved in important infections in dogs. Treatment of dogs with either ERF may have several benefits over treatment with doxycycline alone.
Topics: Acrylates; Administration, Oral; Animals; Anti-Bacterial Agents; Chemistry, Pharmaceutical; Cross-Over Studies; Dogs; Doxycycline; Female; Half-Life; Male; Microbial Sensitivity Tests; Polymethacrylic Acids
PubMed: 25815578
DOI: 10.2460/ajvr.76.4.367 -
Thorax Apr 1976The concentration of doxycycline hydrochloride was measured in serum and bronchial secretions in five patients with chronic bronchitis receiving doxycycline orally in... (Comparative Study)
Comparative Study Review
The concentration of doxycycline hydrochloride was measured in serum and bronchial secretions in five patients with chronic bronchitis receiving doxycycline orally in normal therapeutic dosage for seven days (200 mg day 1, 100 mg days 2 to 7). After the loading dose of 200 mg, serum concentrations ranged between 5-40 and 3-45 mug/ml (mean 4-33 mug/ml) at 3 hours, declining to between 2-28 and 1-21 mug/ml (mean 1-71 mug/ml) at 23 hours. The mean serum levels for days 2 to 7 were 2-15, 1-79, and 1-38 at 3, 8, and 23 hours respectively. There was considerable individual variability and a wide range of concentrations of doxycycline in the sputum (0-07 to 2-10 mug/ml, mean 0-34 mug/ml). During the course of treatment there was a progressive increase in sputum levels and sputum/serum concentration ratios. There was no correlation between sputum concentration and degree of purulence. The clinical efficacy of doxycycline does not appear to be related to sputum concentration, although the progressive increase in sputum doxycycline levels may be relevant in preventing recurrence of acute infection when the drug is administered as long-term prophylactic therapy.
Topics: Bacillus cereus; Bronchitis; Chronic Disease; Doxycycline; Haemophilus influenzae; Humans; Sputum
PubMed: 821169
DOI: 10.1136/thx.31.2.144 -
The Cochrane Database of Systematic... Jun 2021Posterior blepharitis is common and causes ocular surface and lid damage as well as discomfort. It affects 37% to 47% of all ophthalmology patients; its incidence...
BACKGROUND
Posterior blepharitis is common and causes ocular surface and lid damage as well as discomfort. It affects 37% to 47% of all ophthalmology patients; its incidence increasing with age. It is a multifactorial disease associated with multiple other pathologies, such as rosacea, meibomianitis, and infections. Treatment usually focuses on reliefing the symptoms by using artificial tears, lid scrubs, and warm compresses. The condition may be notoriously difficult to manage adequately once it becomes chronic. One such management approach for chronic blepharitis is the use of oral antibiotics for both their antibacterial as well as anti-inflammatory properties. There are currently no guidelines regarding the use of oral antibiotics, including antibiotic type, dosage, and treatment duration, for the treatment of chronic blepharitis.
OBJECTIVES
To assess the benefits and harms of oral antibiotic use for people with chronic blepharitis.
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (which contains the Cochrane Eyes and Vision Trials Register) (2020, Issue 8); Ovid MEDLINE; Embase.com; PubMed; Latin American and Caribbean Health Sciences Literature Database (LILACS); ClinicalTrials.gov, and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP). We did not use any date or language restrictions in the electronic search for trials. We last searched the electronic databases on 29 August 2020.
SELECTION CRITERIA
We included randomized controlled trials (RCTs) comparing oral antibiotics with placebo in adult participants with chronic blepharitis (including staphylococcal, seborrhoeic, or Meibomian Gland Dysfunction (MGD)).
DATA COLLECTION AND ANALYSIS
We used standard Cochrane methodology and graded the certainty of the body of evidence for six outcomes using the GRADE classification.
MAIN RESULTS
We included two studies with 220 participants (numbers of eyes unclear). One parallel-group RCT comparing oral doxycycline (40 mg once a day) with placebo enrolled 70 participants with blepharitis and facial rosacea in the USA. Follow-up duration was three months. One three-arm RCT conducted in South Korea investigated the effect of high-dose (200 mg twice a day) and low-dose (20 mg twice a day) doxycycline versus placebo after one month of study medication. It enrolled 50 participants with chronic MGD in each study arm (i.e. 150 participants enrolled in total). The two studies did not evaluate the same outcome measurements, which precluded any meta-analysis. The evidence for the effect of oral antibiotics on subjective improvement in symptoms was very uncertain. One study suggested that there was little to no effect of oral doxycycline on subjective symptoms based on the Ocular Surface Disease Index (OSDI) scores ranging from 0 to 100 (higher score indicates worse condition) (mean difference (MD) 3.55, 95% confidence interval (CI) -4.61 to 11.71; n = 70) and bulbar conjunctival hyperemia ranging from 0 (clear) to 4 (severe) (MD -0.01, 95% CI -0.38 to 0.36; n = 70) at 12 weeks. The three-arm RCT showed that oral doxycycline may slightly improve number of symptoms (MD -0.56, 95% CI -0.95 to -0.17; n = 93 (high-dose doxycycline versus placebo); MD -0.48, 95% CI -0.86 to -0.10; n = 93 (low-dose doxycycline versus placebo)) and proportion of participants with symptom improvement (risk ratio (RR) 6.13, 95% CI 2.61 to 14.42; n = 93 (high-dose doxycycline versus placebo); RR 6.54, 95% CI 2.79 to 15.30; n = 93 (low-dose doxycycline versus placebo)) at one month, but the evidence is very uncertain. We judged the certainty of evidence for subjective symptoms as very low. One study evaluated aqueous tear production by Schirmer's test (mm/5 min) (higher score indicates better condition) and tear film stability by measuring tear film break-up time (TBUT) in seconds (higher score indicates better condition) at one month. We found very low certainty evidence that oral doxycycline may improve these clinical signs. The estimated MD in Schirmer's test score after one month of treatment was 4.09 mm (95% CI 2.38 to 5.80; n = 93) in the high-dose doxycycline group versus the placebo group and 3.76 mm (95% CI 1.85 to 5.67; n = 93) in the low-dose doxycycline group versus the placebo group. The estimated MD in TBUT after one month was 1.58 seconds (95% CI 0.57 to 2.59; n = 93) when comparing the high-dose doxycycline group with the placebo group, and 1.70 seconds (95% CI 0.96 to 2.44; n = 93) when comparing the low-dose doxycycline group with the placebo group. Although there was a noted improvement in these scores, their clinical importance remains uncertain. One study suggested that oral doxycycline may increase the incidence of serious side effects: 18 (39%) participants in the high-dose doxycycline group, 8 (17%) in the low-dose doxycycline group, and 3 (6%) out of 47 participants in the placebo group experienced serious side effects (RR 6.13, 95% CI 1.94 to 19.41; n = 93 (high-dose doxycycline versus placebo); RR 2.72, 95% CI 0.77 to 9.64; n = 93 (low-dose doxycycline versus placebo)). Additionally, one study reported that one case of migraine headache and five cases of headache were observed in the oral doxycycline group, and one case of non-Hodgkin's lymphoma was observed in the placebo group. We judged the certainty of evidence for adverse events as very low.
AUTHORS' CONCLUSIONS
There was insufficient evidence to draw any meaningful conclusions on the use of oral antibiotics for chronic blepharitis. Very low certainty evidence suggests that oral antibiotics may improve clinical signs, but may cause more adverse events. The evidence for the effect of oral antibiotics on subjective symptoms is very uncertain. Further trials are needed to provide high quality evidence on the use of oral antibiotics in the treatment of chronic blepharitis.
Topics: Administration, Oral; Adult; Anti-Bacterial Agents; Bias; Blepharitis; Chronic Disease; Doxycycline; Drug Administration Schedule; Humans; Randomized Controlled Trials as Topic
PubMed: 34107053
DOI: 10.1002/14651858.CD013697.pub2 -
Advances in Pharmacological and... 2021Persistent postmarket quality evaluation helps produce clear information on the current quality status of the different brands of a given drug and hence introduces a...
BACKGROUND
Persistent postmarket quality evaluation helps produce clear information on the current quality status of the different brands of a given drug and hence introduces a biopharmaceutical and therapeutically equivalent list of the products to the prescribers and users of it. This in turn facilitates access to essential medicines by breaking the high-cost barrier imposed by a few expensive brands of the product. This study was aimed at determining the quality and evaluating the equivalence of doxycycline hyclate capsules and tablets in Jimma, Ethiopia.
METHODS
Ten brands of doxycycline hyclate capsules and tablets were tested for product identity, dosage uniformity, assay, and dissolution; and tablets were tested for friability and hardness.
RESULTS
All investigated brands of doxycycline complied with the USP for dosage uniformity, an assay of the active ingredient, and single-point dissolution tests. One brand, D09, failed both hardness and friability tests. Comparisons of dissolution profiles applying fit factors confirmed that only brands D04, D06, and D07 had similarities with the innovator. Ratio test approaches also showed that significant variability exists between test products and comparators. Weibull model was found to provide the best adjustment curve for all brands, from model-dependent approaches employed for explaining the overall release of drug from the dosage forms.
CONCLUSIONS
Doxycycline is a biowaiver product. Hence, dissolution evaluation suffices its market approval. In this quality assessment study, however, the samples passed quality control tests, except D09 brand which failed friability; it has been revealed that five out of eight brands had problems with interchangeability. Only three doxycycline hyclate brands were found to be equivalent to the comparators.
PubMed: 33629067
DOI: 10.1155/2021/6645876 -
Advances in Clinical and Experimental... Dec 2022Platelets play a fundamental role in myocardial infarction and the pathogenesis of ischemia/reoxygenation (I/R) injuries. They contain matrix metalloproteinases (MMPs)...
BACKGROUND
Platelets play a fundamental role in myocardial infarction and the pathogenesis of ischemia/reoxygenation (I/R) injuries. They contain matrix metalloproteinases (MMPs) that are involved in arterial thrombosis. The MMP inhibitor doxycycline has been shown to exert protective effects in I/R injuries involving various organs and mechanisms.
OBJECTIVES
To explore the influence of doxycycline on platelet activation and MMP-2 activity during I/R.
MATERIAL AND METHODS
Platelets isolated from the blood of healthy human volunteers were subjected to chemical I/R conditions. The study included aerobic controls (AERO), I/R platelets and I/R platelets pretreated with doxycycline (I/R+D). The concentration of doxycycline used was standardized to 10 μM. The analysis of platelet activation markers and platelet microvesicles (PMVs) was performed using flow cytometry. Adenosine diphosphate (ADP)-induced and collagen-induced aggregation, as well as MMP-2 activity and its concentration in platelets were evaluated.
RESULTS
Doxycycline decreased the expression of activated glycoprotein IIb/IIIa on platelets (p = 0.043). Additionally, an increased expression of CD63 was observed in buffers containing PMVs after doxycycline administration (p = 0.043). The ADP-dependent aggregation of I/R platelets was significantly lower in comparison to AERO (p = 0.022). Furthermore, there was a stronger tendency of enhanced ADP-dependent aggregation in I/R platelets pretreated with doxycycline compared to platelets that underwent I/R without doxycycline. Higher MMP-2 activity was observed in I/R+D platelets compared to I/R platelets (p < 0.01).
CONCLUSIONS
The inhibition of platelet MMP-2 by doxycycline attenuated platelet activation and protected platelets by preserving their aggregation ability.
Topics: Humans; Adenosine Diphosphate; Blood Platelets; Doxycycline; Ischemia; Matrix Metalloproteinase 2; Platelet Activation; Platelet Aggregation; Platelet Glycoprotein GPIIb-IIIa Complex; Matrix Metalloproteinase Inhibitors
PubMed: 36135815
DOI: 10.17219/acem/152286 -
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 -
Indian Journal of Pharmaceutical... 2015A simple, rapid, reliable, robust and optimized reversed phase high performance liquid chromatographic method for simultaneous estimation of doxycycline hyclate and...
A simple, rapid, reliable, robust and optimized reversed phase high performance liquid chromatographic method for simultaneous estimation of doxycycline hyclate and curcumin was successfully developed and validated as per International Conference on Harmonization guidelines. The objective was achieved in terms of well separated peaks within 10 min on a Waters Sunfire C8 column with dimensions of 250×4.6 mm, particle size 5.0 μm using mobile phase consisting of 30 volumes of potassium dihydrogen phosphate buffer (50 mM) adjusted to pH 6.5±0.1 with triethylamine and 70 volumes of methanol at flow rate of 0.85 ml/min. The column effluents were monitored at 400 nm maintained at ambient column temperature (28(o)). The developed method was found linear over the concentration range of 200-700 μg/ml for doxycycline hyclate and 8-28 μg/ml for curcumin, the detection and quantitation limit was found to be 26.063 and 78.97 μg/ml for doxycycline hyclate; 0.795 and 2.13 μg/ml for curcumin, respectively. The developed method was optimized using Minitab software version 16 to meet the current quality by design requirements. The method validation was done for linearity, range, detection and quantitation limit, accuracy, precision, specificity, system suitability testing, and robustness.
PubMed: 26997700
DOI: 10.4103/0250-474x.174992 -
Journal of the American Association For... 2016Despite the extensive use of doxycycline in tetracycline-inducible rodent models, little is known regarding its stability in feed or water or the most effective route or...
Despite the extensive use of doxycycline in tetracycline-inducible rodent models, little is known regarding its stability in feed or water or the most effective route or dose. We assessed the concentrations of doxycycline in reverse-osmosis-purified (RO; pH 6.0) and acidified RO (pH 2.6) water in untinted or green-tinted bottles. Doxycycline remained stable in all groups for 7 d and in acidified water in untinted bottles for 14 d. Fungal growth occurred in nonacidified water in tinted and untinted bottles by 12 and 14 d, respectively, and in tinted bottles containing acidified water on day 14, but not in untinted bottles with acidified water. Doxycycline concentrations were also assessed before and at various points after the pelleting of feed from 2 vendors. Each batch was divided for storage at 4 °C, at room temperature, or within ventilated mouse isolator cages and then sampled monthly for 6 mo. Drying caused the greatest decline in doxycycline concentration, whereas γ-irradiation plus shipping and storage condition had minimal effect. Two mouse lines with tetracycline-inducible promoters received 25, 150, or 467 μg/mL or 2 mg/mL doxycycline in water and 200 or 625 ppm in feed before analysis of GFP expression. GFP was expressed in Rosa-rtTA2 mice at 150 μg/mL, whereas Cags-rtTA3 mice required 25 μg/mL. These studies indicate that 1) doxycycline-compounded feed can be handled in the same manner as standard rodent feed, 2) tinted water bottles are not necessary for maintaining drug concentrations, and 3) concentrations lower than those used typically may be effective in lines with tetracycline-inducible promoters.
Topics: Animal Feed; Animals; Anti-Bacterial Agents; Doxycycline; Female; Male; Mice; Mice, Inbred C57BL; Tetracycline; Water
PubMed: 27423155
DOI: No ID Found