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Journal of Veterinary Pharmacology and... Nov 2021The study aims to describe the pharmacokinetics of doxycycline after a single intravenous and oral dose (20 mg/kg) in geese. In addition, two multiple-dose simulations...
The study aims to describe the pharmacokinetics of doxycycline after a single intravenous and oral dose (20 mg/kg) in geese. In addition, two multiple-dose simulations have been performed to investigate the predicted plasma concentration after either a 10 or 20 mg/kg daily administration repeated consecutively for 5 days. Ten geese were enrolled in a two-phase cross-over study with a washout period of two weeks. All animals were treated intravenously and orally with doxycycline, and blood samples were collected up to 48 h after drug administration. Sample analysis was performed using a validated HPLC-UV method. A non-compartmental approach was used to evaluate the pharmacokinetic parameters of the drug. A long elimination half-life was observed (13 h). The area under the curve was statistically different between the two treatments, with the oral bioavailability being moderate (43%). The pharmacokinetic/pharmacodynamic index (%T>MIC) during the 48 h treatment period in the present study (71%) suggests that doxycycline appears to have therapeutic efficacy against some Mycoplasma species in the goose. The multiple-dose simulations showed a low accumulation index. A dosage of 10 mg/kg/day for 5 days seemed to be adequate for a good therapeutic efficacy without reaching unnecessarily high plasma concentrations.
Topics: Administration, Oral; Animals; Area Under Curve; Cross-Over Studies; Doxycycline; Geese; Half-Life
PubMed: 34318509
DOI: 10.1111/jvp.13002 -
American Journal of Respiratory and... Sep 2023Chronic obstructive pulmonary disease (COPD) exacerbations are a major cause of morbidity and mortality, and preventing them is a key treatment target. Long-term... (Randomized Controlled Trial)
Randomized Controlled Trial
Chronic obstructive pulmonary disease (COPD) exacerbations are a major cause of morbidity and mortality, and preventing them is a key treatment target. Long-term macrolide treatment is effective at reducing exacerbations, but there is a paucity of evidence for other antibiotic classes. To assess whether 12-month use of doxycycline reduces the exacerbation rate in people with COPD. People with moderate to very severe COPD and an exacerbation history were recruited from three UK centers and randomized to 12 months of doxycycline 100 mg once daily or placebo. The primary study outcome was the exacerbation rate per person-year. A total of 222 people were randomized. Baseline mean FEV was 1.35 L (SD, 0.35 L), 52.5% predicted (SD, 15.9% predicted). The median number of treated exacerbations in the year before the study was 2 (SD, 1-4). A total of 71% of patients reported two or more exacerbations, and 81% were already prescribed inhaled corticosteroids at baseline. The COPD exacerbation rate did not differ between the groups (doxycycline/placebo rate ratio [RR], 0.86; 95% confidence interval [CI], 0.67-1.10; = 0.23). No difference was seen if only treated exacerbations or hospitalizations were considered. In preplanned subgroup analysis, doxycycline appeared to better reduce the exacerbation rate among people with severe COPD (RR, 0.36; 95% CI, 0.15-0.85; = 0.019) and in those with an eosinophil count <300 cells/μl (RR, 0.50; 95% CI, 0.29-0.84; = 0.01). Health status measured by St. George's Respiratory Questionnaire was 5.2 points worse in the doxycycline group at 12 months ( < 0.007). Doxycycline did not significantly reduce the exacerbation rate, over 12 months, in participants with COPD who exacerbated regularly, but it may have benefitted those with more severe COPD or blood eosinophil counts <300 cells/μl. Clinical trial registered with www.clinicaltrials.gov (NCT02305940).
Topics: Humans; Doxycycline; Anti-Bacterial Agents; Eosinophils; Adrenal Cortex Hormones; Pulmonary Disease, Chronic Obstructive; Double-Blind Method; Disease Progression
PubMed: 37450935
DOI: 10.1164/rccm.202212-2287OC -
Journal of Materials Chemistry. B Feb 2019Biomolecule-nanoparticle hybrids have proven to be one of most promising frontiers in biomedical research. In recent years, there has been an increased focus on the... (Review)
Review
Biomolecule-nanoparticle hybrids have proven to be one of most promising frontiers in biomedical research. In recent years, there has been an increased focus on the development of hybrid lipid-nanoparticle complexes (HLNCs) which inherit unique properties of both the inorganic nanoparticles and the lipid assemblies (i.e. liposomes, lipoproteins, solid lipid nanoparticles, and nanoemulsions) that comprise them. In combination of their component parts, HLNCs also gain new functionalities which are utilized for numerous biomedical applications (i.e. stimuli-triggered drug release, photothermal therapy, and bioimaging). The localization of nanoparticles within the lipid assemblies largely dictates the attributes and functionalities of the hybrid complexes and are classified as such: (i) liposomes with surface-bound nanoparticles, (ii) liposomes with bilayer-embedded nanoparticles, (iii) liposomes with core-encapsulated nanoparticles, (iv) lipid assemblies with hydrophobic core-encapsulated nanoparticles, and (v) lipid bilayer-coated nanoparticles. Herein, we review the properties of each hybrid and the rational design of HLNCs for biomedical applications as reported by recent investigations. Future directions in advancing and expanding the scope of HLNCs are also proposed.
Topics: Biomimetics; Chitosan; Doxycycline; Drug Carriers; Humans; Hydrophobic and Hydrophilic Interactions; Lipid Bilayers; Liposomes; Nanoparticles
PubMed: 30740226
DOI: 10.1039/C8TB03084G -
JAMA Ophthalmology Nov 2022Mild thyroid-associated ophthalmopathy (TAO) negatively impacts quality of life, yet no clinical guidelines for its treatment are available. Existing evidence supports...
IMPORTANCE
Mild thyroid-associated ophthalmopathy (TAO) negatively impacts quality of life, yet no clinical guidelines for its treatment are available. Existing evidence supports the use of doxycycline in treating mild TAO.
OBJECTIVE
To evaluate the short-term (12 weeks) efficacy of doxycycline in treating mild TAO.
DESIGN, SETTING, AND PARTICIPANTS
In this placebo-controlled multicenter randomized double-masked trial, 148 patients were assessed for eligibility. After exclusions (patients who were pregnant or lactating, had an allergy to tetracyclines, or had uncontrolled systematic diseases), 100 patients with mild TAO (orbital soft tissue affected mildly) at 5 centers in China were enrolled from July 2013 to December 2019 and monitored for 12 weeks.
INTERVENTIONS
Participants were randomly assigned 1:1 to receive doxycycline (50 mg) or placebo once daily for 12 weeks.
MAIN OUTCOMES AND MEASURES
The primary outcome was the rate of improvement at 12 weeks compared with baseline assessed by a composite indicator of eyelid aperture (reduction ≥2 mm), proptosis (reduction ≥2 mm), ocular motility (increase ≥8°), and Graves ophthalmopathy-specific quality-of-life (GO-QOL) scale score (increase ≥6 points). Adverse events were recorded.
RESULTS
A total of 50 participants were assigned to doxycycline and 50 to placebo. The mean (SD) age was 36.7 (9.1) years; 75 participants (75.0%) were female and 100 (100.0%) were Asian. Medication compliance was checked during participant interviews and by counting excess tablets. At week 12, the improvement rate was 38.0% (19 of 50) in the doxycycline group and 16.0% (8 of 50) in the placebo group (difference, 22.0%; 95% CI, 5.0-39.0; P = .01) in the intention-to-treat population. The per-protocol sensitivity analysis showed similar results (39.6% [19 of 48] vs 16.0% [8 of 50]; difference, 23.6%; 95% CI, 6.4-40.8; P = .009). No adverse events other than 1 case of mild gastric acid regurgitation was recorded in either group.
CONCLUSIONS AND RELEVANCE
The results of this study indicate that oral doxycycline, 50 mg daily, resulted in greater improvement of TAO-related symptoms at 12 weeks compared with placebo in patients with mild TAO. These findings support the consideration of doxycycline for mild TAO but should be tempered by recognizing the relatively short follow-up and the size of the cohort.
TRIAL REGISTRATION
ClinicalTrials.gov Identifier: NCT02203682.
Topics: Humans; Female; Adult; Male; Doxycycline; Graves Ophthalmopathy; Quality of Life; Lactation; Anti-Bacterial Agents; Double-Blind Method
PubMed: 36173609
DOI: 10.1001/jamaophthalmol.2022.3779 -
Hong Kong Medical Journal = Xianggang... Jun 2024
Topics: Humans; Doxycycline; Anti-Bacterial Agents; Male; Female; Middle Aged
PubMed: 38618912
DOI: 10.12809/hkmj2310708 -
JCI Insight Nov 2022Rosacea is a chronic skin disorder characterized by abnormal neurovascular and inflammatory conditions on the central face. Despite increasing evidence suggesting that...
Rosacea is a chronic skin disorder characterized by abnormal neurovascular and inflammatory conditions on the central face. Despite increasing evidence suggesting that rosacea is associated with metabolic disorders, the role of metabolism in rosacea pathogenesis remains unknown. Here, via a targeted metabolomics approach, we characterized significantly altered metabolic signatures in patients with rosacea, especially for amino acid-related metabolic pathways. Among these, glutamic acid and aspartic acid were highlighted and positively correlated with the disease severity in patients with rosacea. We further demonstrated that glutamic acid and aspartic acid can facilitate the development of erythema and telangiectasia, typical features of rosacea, in the skin of mice. Mechanistically, glutamic acid and aspartic acid stimulated the production of vasodilation-related neuropeptides from peripheral neurons and keratinocytes and induced the release of nitric oxide from endothelial cells and keratinocytes. Interestingly, we provided evidence showing that doxycycline can improve the symptoms of patients with rosacea possibly by targeting the amino acid metabolic pathway. These findings reveal that abnormal amino acid metabolism promotes neurovascular reactivity in rosacea and raise the possibility of targeting dysregulated metabolism as a promising strategy for clinical treatment.
Topics: Animals; Mice; Endothelial Cells; Aspartic Acid; Glutamic Acid; Rosacea; Doxycycline
PubMed: 36219476
DOI: 10.1172/jci.insight.161870 -
The Cochrane Database of Systematic... Sep 2018Scrub typhus, an important cause of acute fever in Asia, is caused by Orientia tsutsugamushi, an obligate intracellular bacterium. Antibiotics currently used to treat... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Scrub typhus, an important cause of acute fever in Asia, is caused by Orientia tsutsugamushi, an obligate intracellular bacterium. Antibiotics currently used to treat scrub typhus include tetracyclines, chloramphenicol, macrolides, and rifampicin.
OBJECTIVES
To assess and compare the effects of different antibiotic regimens for treatment of scrub typhus.
SEARCH METHODS
We searched the following databases up to 8 January 2018: the Cochrane Infectious Diseases Group specialized trials register; CENTRAL, in the Cochrane Library (2018, Issue 1); MEDLINE; Embase; LILACS; and the metaRegister of Controlled Trials (mRCT). We checked references and contacted study authors for additional data. We applied no language or date restrictions.
SELECTION CRITERIA
Randomized controlled trials (RCTs) or quasi-RCTs comparing antibiotic regimens in people with the diagnosis of scrub typhus based on clinical symptoms and compatible laboratory tests (excluding the Weil-Felix test).
DATA COLLECTION AND ANALYSIS
For this update, two review authors re-extracted all data and assessed the certainty of evidence. We meta-analysed data to calculate risk ratios (RRs) for dichotomous outcomes when appropriate, and elsewhere tabulated data to facilitate narrative analysis.
MAIN RESULTS
We included six RCTs and one quasi-RCT with 548 participants; they took place in the Asia-Pacific region: Korea (three trials), Malaysia (one trial), and Thailand (three trials). Only one trial included children younger than 15 years (N = 57). We judged five trials to be at high risk of performance and detection bias owing to inadequate blinding. Trials were heterogenous in terms of dosing of interventions and outcome measures. Across trials, treatment failure rates were low.Two trials compared doxycycline to tetracycline. For treatment failure, the difference between doxycycline and tetracycline is uncertain (very low-certainty evidence). Doxycycline compared to tetracycline may make little or no difference in resolution of fever within 48 hours (risk ratio (RR) 1.14, 95% confidence interval (CI) 0.90 to 1.44, 55 participants; one trial; low-certainty evidence) and in time to defervescence (116 participants; one trial; low-certainty evidence). We were unable to extract data for other outcomes.Three trials compared doxycycline versus macrolides. For most outcomes, including treatment failure, resolution of fever within 48 hours, time to defervescence, and serious adverse events, we are uncertain whether study results show a difference between doxycycline and macrolides (very low-certainty evidence). Macrolides compared to doxycycline may make little or no difference in the proportion of patients with resolution of fever within five days (RR 1.05, 95% CI 0.99 to 1.10; 185 participants; two trials; low-certainty evidence). Another trial compared azithromycin versus doxycycline or chloramphenicol in children, but we were not able to disaggregate date for the doxycycline/chloramphenicol group.One trial compared doxycycline versus rifampicin. For all outcomes, we are uncertain whether study results show a difference between doxycycline and rifampicin (very low-certainty evidence). Of note, this trial deviated from the protocol after three out of eight patients who had received doxycycline and rifampicin combination therapy experienced treatment failure.Across trials, mild gastrointestinal side effects appeared to be more common with doxycycline than with comparator drugs.
AUTHORS' CONCLUSIONS
Tetracycline, doxycycline, azithromycin, and rifampicin are effective treatment options for scrub typhus and have resulted in few treatment failures. Chloramphenicol also remains a treatment option, but we could not include this among direct comparisons in this review.Most available evidence is of low or very low certainty. For specific outcomes, some low-certainty evidence suggests there may be little or no difference between tetracycline, doxycycline, and azithromycin as treatment options. Given very low-certainty evidence for rifampicin and the risk of inducing resistance in undiagnosed tuberculosis, clinicians should not regard this as a first-line treatment option. Clinicians could consider rifampicin as a second-line treatment option after exclusion of active tuberculosis.Further research should consist of additional adequately powered trials of doxycycline versus azithromycin or other macrolides, trials of other candidate antibiotics including rifampicin, and trials of treatments for severe scrub typhus. Researchers should standardize diagnostic techniques and reporting of clinical outcomes to allow robust comparisons.
Topics: Adult; Anti-Bacterial Agents; Azithromycin; Child, Preschool; Chloramphenicol; Doxycycline; Humans; Macrolides; Randomized Controlled Trials as Topic; Rifampin; Scrub Typhus; Tetracycline
PubMed: 30246875
DOI: 10.1002/14651858.CD002150.pub2 -
Lakartidningen Nov 2017
Topics: Child; Doxycycline; Drug-Related Side Effects and Adverse Reactions; Humans; Iatrogenic Disease; Sweden; Tooth Discoloration
PubMed: 29292912
DOI: No ID Found -
Topics in Antiviral Medicine Dec 2023Doxycycline postexposure prophylaxis (doxy-PEP) is a novel strategy now demonstrated in several clinical trials to dramatically reduce incidence rates of gonorrhea,... (Review)
Review
Doxycycline postexposure prophylaxis (doxy-PEP) is a novel strategy now demonstrated in several clinical trials to dramatically reduce incidence rates of gonorrhea, chlamydia, and syphilis in some key populations at high risk of sexually transmitted infections. Even so, much remains unknown about the long-term consequences of doxy-PEP, and several concerns, including the potential for the development of antibiotic resistance and disturbances to the microbiome, balance the benefits. This review highlights the history of antibiotic prophylaxis for sexually transmitted infections, and the rationale, current evidence, and future directions for doxy-PEP.
Topics: Humans; Doxycycline; Sexually Transmitted Diseases; Syphilis; Gonorrhea; Antibiotic Prophylaxis
PubMed: 38198668
DOI: No ID Found -
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