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Journal of Pharmaceutical and... Sep 2018Concentrated solutions of doxycycline are often added to drinking water of animals for oral antibiotic therapy. However, stability concerns of doxycycline in solution...
Concentrated solutions of doxycycline are often added to drinking water of animals for oral antibiotic therapy. However, stability concerns of doxycycline in solution involve an accurate selection of the solvent system to ensure that the active substance will remain within the acceptance range during the product shelf-life and to avoid sub-therapeutic dosage. Different solvent systems have been evaluated in order to determine their influence on the stability of concentrated doxycycline solutions. The results showed differences in the degradation kinetics of doxycycline depending on the co-solvent used and they permitted to select a solvent system for liquid doxycycline hyclate formulations with low rate of degradation even after several months of storage. So, the inclusion of ethanol together with propylene glycol as main excipient was found to be beneficial, while no benefit was observed concerning the addition of citric acid. Once administered to drinking water, the solutions were stable for 24 h with no influence of the solvent system.
Topics: Chromatography, High Pressure Liquid; Doxycycline; Drinking Water; Drug Stability; Pharmaceutical Solutions; Solvents
PubMed: 29980020
DOI: 10.1016/j.jpba.2018.06.054 -
Acta Veterinaria Scandinavica Jun 2012Based on its PK/PD ratios, doxycycline hyclate (DOX-h), a time-dependant antibacterial, is ideally expected to achieve both sustained plasma drug concentrations at or...
Based on its PK/PD ratios, doxycycline hyclate (DOX-h), a time-dependant antibacterial, is ideally expected to achieve both sustained plasma drug concentrations at or slightly above the MIC level for as long as possible between dosing intervals. Pursuing this end, a poloxamer-based matrix was used to produce a long-acting injectable preparation (DOX-h-LA) and its serum concentrations vs. time profile investigated after its SC injection to dogs (≤ 0.3 mL per injection site), and results compared with the oral (PO) and IV pharmacokinetics of DOX-h, prepared as tablet or as freshly made solution. A crossover (4 x 4 x 4) study design was employed with 12 Mongrel dogs, with washout periods of 21 days, and at dose of 10 mg/kg in all cases. DOX-h-LA showed the greatest values for bioavailability (199.48%); maximum serum concentration (Cmax) value was 2.8 ± 0.3 with a time to reach Cmax (Tmax) of 2.11 ± 0.12 h and an elimination half-life of 133.61 ± 6.32 h. Considering minimum effective serum concentration of 0.5 μg/mL, a dose-interval of at least 1 week h can be achieved for DOX-h-LA, and only 48 h and 24 h after the IV or PO administration of DOX-h as a solution or as tablets, respectively. A non-painful small bulge, apparently non-inflammatory could be distinguished at injection sites. These lumps dissipated completely in 30 days in all cases.
Topics: Administration, Oral; Animals; Anti-Bacterial Agents; Area Under Curve; Biological Availability; Cross-Over Studies; Dogs; Doxycycline; Female; Half-Life; Injections, Intravenous; Injections, Subcutaneous; Male; Poloxamer; Tablets
PubMed: 22682068
DOI: 10.1186/1751-0147-54-35 -
Journal of Feline Medicine and Surgery Aug 2005
Topics: Animals; Anti-Bacterial Agents; Bacterial Infections; Cat Diseases; Cats; Doxycycline; Endoscopy; Esophageal Stenosis
PubMed: 16055011
DOI: 10.1016/j.jfms.2005.05.002 -
Journal of Labelled Compounds &... Jun 2016A stable isotope labelled mass spectrometry internal standard of the antibiotic doxycycline was prepared to assist in pharmacokinetic analyses. Our approach was to first...
A stable isotope labelled mass spectrometry internal standard of the antibiotic doxycycline was prepared to assist in pharmacokinetic analyses. Our approach was to first N-demethylate doxycycline using a non-classical Polonovski reaction and then re-methylate using methyl-[(13) CD3 ] iodide, which gave doxycycline-[(13) CD3 ] with an isotopic purity of 99%.
Topics: Chemistry Techniques, Synthetic; Doxycycline; Isotope Labeling; Radiochemistry; Reference Standards
PubMed: 27061598
DOI: 10.1002/jlcr.3397 -
Talanta Jan 2024The simultaneous balance of electrode materials and electrode structures can energize the development of innovative electrochemical sensors. In this work, a 3D...
The simultaneous balance of electrode materials and electrode structures can energize the development of innovative electrochemical sensors. In this work, a 3D nanocarbon layer of hybrid heteroatoms and metal atoms (CN/Fe) with excellent electrical properties and abundant active sites was self-constructed on the surface of a quartz-based nanofiber by high-temperature pyrolysis. Further, the nanofiber tip was selected as the sensing region to develop an electrochemical sensing platform with high sensitivity, miniaturization, and portability. A common broad-spectrum antibiotic (Doxycycline hyclate, DOX) was used as a model to evaluate the designed miniaturized sensing platform, and the stability, reproducibility, and applicability of the microsensor were verified in a variety of real samples, including algal solution, milk, human serum, and cell culture media. The results show that the proposed sensing platform has a detection limit as low as 82 nM in aqueous environments. Furthermore, it is further shown that coupling the design of electrode materials and electrode structures facilitates the development of electrochemical sensors with more practical applications. This concept will open up new avenues for the development of electrochemical sensors that meet many application scenarios.
Topics: Female; Humans; Microelectrodes; Doxycycline; Reproducibility of Results; Electrochemical Techniques; Nanofibers
PubMed: 37478766
DOI: 10.1016/j.talanta.2023.124926 -
Cutis Feb 2010There is a paucity of treatment options for severe acne vulgaris aside from oral isotretinoin. This randomized, vehicle-controlled, multicenter, double-blind study... (Randomized Controlled Trial)
Randomized Controlled Trial
Effective and safe combination therapy for severe acne vulgaris: a randomized, vehicle-controlled, double-blind study of adapalene 0.1%-benzoyl peroxide 2.5% fixed-dose combination gel with doxycycline hyclate 100 mg.
There is a paucity of treatment options for severe acne vulgaris aside from oral isotretinoin. This randomized, vehicle-controlled, multicenter, double-blind study evaluated the efficacy and safety of combination therapy using adapalene 0.1%-benzoyl peroxide 2.5% (A/BPO) fixed-dose combination gel with doxycycline hyclate 100 mg in the treatment of severe acne vulgaris. A total of 459 participants were randomized in a 1:1 ratio to receive oral doxycycline hyclate 100 mg once daily and either A/BPO or vehicle once daily for 12 weeks. Efficacy in the A/BPO with doxycycline group was demonstrated as early as week 2 compared with the vehicle arm for total, inflammatory, and noninflammatory lesions (all P < .005). At week 12, this combination was superior to vehicle with doxycycline in reducing total, inflammatory, and noninflammatory lesion counts (an added incremental benefit of 23%, 24%, and 21%, respectively), as well as for global success and overall participant satisfaction (all P < .001). Digital UV fluorescence photography demonstrated a rapid reduction in Propionibacterium acnes in the A/BPO with doxycycline group, particularly within the first 4 weeks. These findings provide evidence on the efficacy of combining A/BPO and the oral antibiotic doxycycline in the treatment of severe acne vulgaris.
Topics: Acne Vulgaris; Adapalene; Administration, Oral; Administration, Topical; Adolescent; Anti-Bacterial Agents; Anti-Inflammatory Agents, Non-Steroidal; Benzoyl Peroxide; Dermatologic Agents; Double-Blind Method; Doxycycline; Drug Combinations; Female; Gels; Humans; Male; Naphthalenes; Pharmaceutical Vehicles
PubMed: 20349684
DOI: No ID Found -
Archives of Oral Biology Feb 2012To characterize the mechanical and biological properties of a resin-modified glass ionomer cement (RMGIC) containing doxycycline hyclate.
OBJECTIVES
To characterize the mechanical and biological properties of a resin-modified glass ionomer cement (RMGIC) containing doxycycline hyclate.
METHODS
The antibacterial effect of RMGIC containing 1.5, 3.0 and 4.5% doxycycline hyclate was assessed using two experiments - agar diffusion test for 24h and biofilm assay for 24h and 7 days - against some cariogenic bacteria. Briefly, base layers of BHI agar and 300μL of each inoculum were prepared in Petri dishes with 6 wells that were completely filled with materials. After 24h incubation, zones of bacterial growth inhibition were measured using a digital caliper. Biofilm assays were conducted using RMGIC specimens immersed in 24-well plates containing the inoculum in BHI broth. After 24h and 7 days, each specimen were removed, vortexed and the suspension diluted and inoculated in BHI plates for subsequent bacterial counting. Cytotoxicity tests used 50 specimens made in sterilized metal molds, including Vitrebond as positive control. Extracts from every specimen were applied on the MDPC-23 odontoblast-like cells for 24h. The MTT assay and SEM evaluation determined cell metabolism and morphology, respectively. 80 cylindrical specimens were made from the previously cited groups, and were submitted to testing with a universal testing machine (Instron 4411) using a crosshead speed of 1.0mm/min for compressive strength and 0.5mm/min for diametral tensile strength, respectively. Data from antibacterial and cytotoxic effects, and mechanical properties were submitted to appropriated statistical tests.
RESULTS
All tested groups showed growth inhibition of all tested strains (p<0.05) in 24h for both microbiological tests, but only 4.5% doxycycline have antibacterial effect after 7 days. None of doxycycline concentrations caused toxic effect to the MDPC-23 cells or presenting alterations to mechanical properties.
CONCLUSION
The incorporation of up to 4.5% doxycycline hyclate into RMGIC inhibits important oral microorganisms, without modifying biological and mechanical characteristics of the dental material, suggesting a new alternative for the treatment of dental caries.
Topics: Anti-Bacterial Agents; Biological Assay; Cell Line; Colony Count, Microbial; Dental Caries; Doxycycline; Glass Ionomer Cements; Microbial Sensitivity Tests; Resin Cements
PubMed: 21920494
DOI: 10.1016/j.archoralbio.2011.08.009 -
International Journal of Experimental... Apr 2013All reports of doxycycline-induced cardiomyopathy to date have been limited to accidental oral poisoning in calves. Therefore, the current study investigated the...
All reports of doxycycline-induced cardiomyopathy to date have been limited to accidental oral poisoning in calves. Therefore, the current study investigated the cardiomyotoxic effect of experimental doxycycline overdose in rats as a toxicity model which could be monitored using histopathological and biochemical assays. A total of 38-week-old male Wistar rats were divided into three groups consisting of 10 each. The first group was an untreated control group (D0 ), and the second group (D5 ) received doxycycline hyclate 25 mg/kg intragastrically twice daily (8 AM and 8 PM), which is 5-fold higher than the standard dose. The third group (D10 ) received 50 mg/kg intragastrically twice daily (8 AM and 8 PM), which is 10-fold higher than the standard dose. The dose continued for 10 consecutive days and revealed that the doxycycline toxicity was dose dependent. Mortality was recorded in the D10 group only (30%). The D5 rats exhibited minimal skeletal muscle injury and slight but significant increases in the skeletal muscle damage indicators creatine kinase (CK) and aspartate aminotransferase (AST) compared to controls. The cardiac muscle of the D5 rats was histologically normal, and the D5 rats also exhibited normal levels of troponin I (cTnI), an indicator of cardiac muscle damage. In contrast, the D10 rats displayed cardiomyopathy, as well as significant increases in the muscle enzymes alanine aminotransferase (ALT), AST and CK and the cardiac damage indicator cTnI compared to control and D5 groups. Pulmonary lesions were observed in the D10 rats, primarily cardiac lesion-related alveolar heart failure cells. Thus the present study is the first to demonstrate that oral doxycycline poisoning (10 times the therapeutic dose)-induced cardiomyopathy is not limited to calves and could occur without any predisposing factors.
Topics: Administration, Oral; Alanine Transaminase; Animals; Anti-Bacterial Agents; Aspartate Aminotransferases; Cardiomyopathies; Creatine Kinase; Disease Models, Animal; Dose-Response Relationship, Drug; Doxycycline; Drug Overdose; Humans; L-Lactate Dehydrogenase; Lung; Male; Muscle, Skeletal; Myocardium; Random Allocation; Rats; Rats, Wistar; Troponin I
PubMed: 23432546
DOI: 10.1111/iep.12013 -
JPEN. Journal of Parenteral and Enteral... 1981To study the effects of intravenous doxycycline hyclate on protein malnourished rats, 20 male Sprague-Dawley rats, weighing 234 to 277 g, were protein depleted for 6...
To study the effects of intravenous doxycycline hyclate on protein malnourished rats, 20 male Sprague-Dawley rats, weighing 234 to 277 g, were protein depleted for 6 weeks then randomly assigned to one of two groups: group I (10 rats), total parenteral nutrition with intravenous doxycycline hyclate injections, group II (10 rats), total parenteral nutrition with normal saline injections. Both groups were then protein repleted for 7 days. Body weight; fluid intake; urine output; liver, spleen, and lung weights; nitrogen content; and serum proteins were measured. The antibiotic dosage given was 10 mg/kg body weight/day or 0.1688 +/- 0.0046 mg/kg. There was no significant difference in starting weight, weight after 6 weeks of protein depletion, weight at sacrifice, or weight gain between groups I and II. Average fluid intake/day for groups I (50 +/- 2 ml) and II (51 +/- 3 ml) were not statistically significant. There was no significant difference in average urine output/day nitrogen balance, liver weight, and liver nitrogen, spleen and lung weights, or serum albumin levels (Groups I, 2.84 +/- 0.48 g%, Group II, 2.72 +/- 0.24 g+). Intravenous doxycycline hyclate does not appear to have a protein catabolic effect on protein malnourished rats receiving total parenteral nutrition.
Topics: Animals; Blood Proteins; Body Weight; Doxycycline; Male; Parenteral Nutrition; Parenteral Nutrition, Total; Protein Deficiency; Proteins; Rats; Rats, Inbred Strains
PubMed: 6801285
DOI: 10.1177/0148607181005006510 -
Journal of Medical Microbiology Apr 2008Current prophylaxis for infected tick bites consists of personal protective measures directed towards ticks. This study compared the efficacy of a single oral dose of...
A sustained-release formulation of doxycycline hyclate (Atridox) prevents simultaneous infection of Anaplasma phagocytophilum and Borrelia burgdorferi transmitted by tick bite.
Current prophylaxis for infected tick bites consists of personal protective measures directed towards ticks. This study compared the efficacy of a single oral dose of doxycycline with that of a single injection of sustained-release doxycycline in a model of Lyme borreliosis and Anaplasma phagocytophilum infection. Dosages of doxycycline were equilibrated based on previously determined peak plasma levels in mice [oral, 2.4 microg (ml plasma)(-1); sustained release, 1.9 microg (ml plasma)(-1)] determined 8 h after inoculation. In challenge experiments where five Borrelia burgdorferi-infected and five A. phagocytophilum-infected nymphs were used per mouse, only 20 and 30 % of mice were protected from B. burgdorferi and A. phagocytophilum infection, respectively, using oral doxycycline. In contrast, 100 % of mice receiving sustained-release doxycycline were protected from A. phagocytophilum infection, as indicated by real-time PCR of blood samples, quantitative PCR and culture isolation of spleen samples, and protected against B. burgdorferi infection as demonstrated by culture of ear, heart and bladder. Although 15-40 copies of A. phagocytophilum could be amplified from the spleens of mice treated with sustained-release doxycycline, no viable A. phagocytophilum from these spleens could be cultured in HL-60 cells. In contrast, 7/10 mice receiving oral doxycycline were PCR- and culture-positive for A. phagocytophilum, with copy numbers ranging from 800 to 10 000 within the spleen, as determined by quantitative PCR. Other correlates with A. phagocytophilum infection included a significant difference in spleen mass (mean of 110 mg for sustained-release treatment versus a mean of 230 mg for oral treatment) and the number of splenic lymphoid nodules (mean of 8 for sustained-release treatment versus mean of 12.5 for oral doxycycline) as determined by histopathology. These studies indicate that a single injection of a sustained-release formulation antibiotic may offer a viable prophylactic treatment option for multiple infectious agents in patients presenting with tick bites.
Topics: Anaplasma phagocytophilum; Animals; Anti-Bacterial Agents; Antibiotic Prophylaxis; Borrelia burgdorferi; Delayed-Action Preparations; Doxycycline; Ehrlichiosis; Female; Humans; Insect Bites and Stings; Ixodes; Lyme Disease; Mice; Mice, Inbred C3H; Treatment Outcome
PubMed: 18349366
DOI: 10.1099/jmm.0.47535-0