The aim of the present study was to determine the pharmacokinetics (PKs) and bioavailability of danofloxacin in chukar partridge (Alectoris chukar) following intravenous (IV), intramuscular (IM), subcutaneous (SC), and oral (PO) administrations at a dose of 10 mg/kg. A total of eight clinically healthy chukar partridges weighing 480 ± 45 g were used for the investigation. The study was performed in a crossover design (2 × 2 × 2 × 2) with a 15‐day washout period between two administrations in four periods. The plasma concentrations of danofloxacin were determined using reversed‐phase high‐performance liquid chromatography. Noncompartmental PK parameters were also estimated. No local or systemic adverse drug effects were observed in any of the chukar partridges. The mean elimination half‐life ranged between 8.18 and 12.08 hr and differed statistically among administration routes. The mean peak plasma concentrations of danofloxacin following IM, SC, and PO administrations were 8.05, 9.58, and 3.39 μg/ml at 0.5, 1, and 4 hr, respectively. Following IM, SC, and PO administrations, the mean bioavailability was 86.33%, 134.40%, and 47.62%, respectively. The mean total clearance and volume of distribution at steady‐state following IV administration were 0.13 L hr−1 kg−1 and 0.96 L/kg, respectively. These data, including favorable PKs and the absence of adverse drug effects, suggest that danofloxacin is a useful antibiotic in chukar partridges.
In the present study, combined treatment with etanercept and anakinra were tested in the streptozotocin-induced diabetic rats. Forty male Wistar albino rats were divided into 5 groups: healthy control (HC), diabetic control (DC), diabetic + anakinra (DAT), diabetic + etanercept (DET), and diabetic + etanercept + anakinra (DEAT). HC and DC groups received subcutaneous (s.c.) injection with a saline solution, while DAT and DET groups received anakinra (10 mg/kg per day, s.c.) or etanercept (10 mg/kg, twice a week, s.c.), and DEAT rats received both anakinra and etanercept treatments for 21 days after diabetes has developed. Anakinra and etanercept treatments significantly increased insulin and homeostatic model assessment β-cell function levels and decreased glucose levels compared to the DC group as single (DAT and DET) and combined treatments (DEAT). The thiobarbituric acid reactive substances level was significantly decreased in DAT group. The combine use of etanercept and anakinra can improve insulin and blood glucose in type 2 diabetic rats. The combined treatment of anakinra and etanercept together was more effective than single treatment and might have a potential new treatment strategy and to reduce the mortality and morbidity resulting from diabetes.
The pharmacokinetics of levofloxacin (4 mg/kg), administered both alone and in combination with tolfenamic acid (2 mg/kg) and flunixin meglumine (2.2 mg/kg), was established after intravenous administration in sheep. Plasma levofloxacin concentrations were assayed by high-performance liquid chromatography and analysed according to the two-compartment open model. Following the administration of levofloxacin alone, the mean distribution half-life, elimination half-life, total clearance, volume of distribution at steady state and area under the plasma concentration–time curve were 0.20 h, 1.82 h, 0.39 L/h/kg, 0.96 L/kg and 10.40 h × µg/mL, respectively. Tolfenamic acid and flunixin meglumine caused a slow elimination and increased plasma concentrations of levofloxacin in combination administration. Levofloxacin, with an alteration in the dosage regimen, can be used effectively with tolfenamic acid and flunixin meglumine for the therapy of infections and inflammatory conditions in sheep.
In this study, the pharmacokinetics of moxifloxacin (5 mg/kg) was determined following a single intravenous administration of moxifloxacin alone and co‐administration with diclofenac (2.5 mg/kg) or flunixin meglumine (2.2 mg/kg) in sheep. Six healthy Akkaraman sheep (2 ± 0.3 years and 53.5 ± 5 kg of body weight) were used. A longitudinal design with a 15‐day washout period was used in three periods. In the first period, moxifloxacin was administered by an intravenous (IV) injection. In the second and third periods, moxifloxacin was co‐administered with IV administration of diclofenac and flunixin meglumine, respectively. The plasma concentration of moxifloxacin was assayed by high‐performance liquid chromatography. The pharmacokinetic parameters were calculated using a two‐compartment open pharmacokinetic model. Following IV administration of moxifloxacin alone, the mean elimination half‐life (t1/2β), total body clearance (ClT), volume of distribution at steady state (Vdss) and area under the curve (AUC) of moxifloxacin were 2.27 hr, 0.56 L h−1 kg−1, 1.66 L/kg and 8.91 hr*µg/ml, respectively. While diclofenac and flunixin meglumine significantly increased the t1/2β and AUC of moxifloxacin, they significantly reduced the ClT and Vdss. These results suggest that anti‐inflammatory drugs could increase the therapeutic efficacy of moxifloxacin by altering its pharmacokinetics.
This study was conducted to determine the passage ratio of amoxicillin into milk and its pharmacokinetics in milk and plasma after intramuscular administration. Five healthy dairy cows (Holstein, weighing 450-500 kg, aged 2-4 years) were used in this study. They received single intramuscular amoxicillin at a dose of 14 mg/kg body weight. Blood and milk samples were collected prior to drug administration (0); after 15, 30, 45, 60, and 90 min; and 2, 3, 4, 6, 8, 10, and 12 hr after administration. The plasma and milk concentrations of amoxicillin were determined using high-performance liquid chromatography with ultraviolet detection. The passage ratio of amoxicillin into milk and plasma was determined using both AUC-based calculation and milk and plasma concentrations at sampling times; it was calculated 0.46 and 0.52, respectively. The terminal half-life and mean residence time of amoxicillin were 6.05 and 8.60 hr in plasma and 2.62 and 5.35 hr in milk, respectively. The C levels of amoxicillin in plasma and milk were measured as 1,096 and 457 ng/ml, respectively. It was observed that amoxicillin exhibited a secondary peak in plasma and milk. This study was the first to report on the passage ratio of amoxicillin into milk in lactating cows.
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