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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 -
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 Translational Medicine Dec 2023Syphilis, a sexually transmitted disease (STD) caused by Treponema pallidum (T. pallidum), has had a worldwide resurgence in recent years and remains a public health... (Review)
Review
Syphilis, a sexually transmitted disease (STD) caused by Treponema pallidum (T. pallidum), has had a worldwide resurgence in recent years and remains a public health threat. As such, there has been a great deal of research into clinical strategies for the disease, including diagnostic biomarkers and possible strategies for treatment and prevention. Although serological testing remains the predominant laboratory diagnostic method for syphilis, it is worth noting that investigations pertaining to the DNA of T. pallidum, non-coding RNAs (ncRNAs), chemokines, and metabolites in peripheral blood, cerebrospinal fluid, and other bodily fluids have the potential to offer novel perspectives on the diagnosis of syphilis. In addition, the global spread of antibiotic resistance, such as macrolides and tetracyclines, has posed significant challenges for the treatment of syphilis. Fortunately, there is still no evidence of penicillin resistance. Hence, penicillin is the recommended course of treatment for syphilis, whereas doxycycline, tetracycline, ceftriaxone, and amoxicillin are viable alternative options. In recent years, efforts to discover a vaccine for syphilis have been reignited with better knowledge of the repertoire of T. pallidum outer membrane proteins (OMPs), which are the most probable syphilis vaccine candidates. However, research on therapeutic interventions and vaccine development for human subjects is limited due to practical and ethical considerations. Thus, the preclinical model is ideal for conducting research, and it plays an important role in clinical transformation. Different preclinical models have recently emerged, such as in vitro culture and mouse models, which will lay a solid foundation for clinical treatment and prevention of syphilis. This review aims to provide a comprehensive summary of the most recent syphilis tactics, including detection, drug resistance treatments, vaccine development, and preclinical models in clinical practice.
Topics: Animals; Mice; Humans; Syphilis; Treponema pallidum; Anti-Bacterial Agents; Doxycycline; Vaccines
PubMed: 38105236
DOI: 10.1186/s12967-023-04685-4 -
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 -
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