Journal of veterinary pharmacology and therapeutics最新文献

The pharmacokinetic features of levamisole were assessed in chukar partridges ( Alectoris chukar ) following intravenous (IV), intramuscular (IM), and subcutaneous (SC) administrations. The investigation included nine male partridges and a crossover pharmacokinetic design. Levamisole was administered to partridges at a dose of 20 mg/kg via IV, IM, and SC routes. Blood samples were collected at time points of 0, 0.25, 0.50, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 18, and 24 h after administrations. Plasma concentrations of levamisole were quantified by high-performance liquid chromatography (HPLC) and evaluated using a non-compartmental analysis. The elimination half-life was 1.92, 2.94, and 2.97 h for IV, IM, and SC administration, respectively. The IV injection for levamisole showed the volume of distribution at a steady state of 1.91 L/kg and total clearance of 0.73 L/h/kg. The peak plasma concentration (C_max) for IM and SC routes of levamisole was 5.32 and 4.65 μg/mL at 0.25 h, respectively. The absolute bioavailability was 66.16% for the IM route and 58.48% for the SC route. The study findings reveal that levamisole administered via IM and SC routes exhibit comparable pharmacokinetic profiles, with both routes achieving bioavailability exceeding 50%. However, the significant adverse effects (muscle tremors, hyperexcitability, and increased respiratory rate) associated with IV administration underscore the need for caution and support the preference for IM and SC routes, which offer better safety profiles for bird anthelmintic treatments.

The present study was conducted to establish population pharmacokinetics (PPK) of florfenicol (FLO) in crayfish (Procambarus clarkii) after a single oral administration at a dose of 15 mg/kg at 25°C based on a nonlinear mixed effect model. The sparse sampling method was used to collect the blood samples. Thirty-two crayfish were divided into four groups, and one group included four male crayfish and four female crayfish. One animal undertook three sampling time points. All samples were quantified using high-performance liquid chromatography with an ultraviolet detector. The initial pharmacokinetic (PK) parameters were estimated by reference search and the calculation of a naïve pooled approach. The additive error model was selected using the tool of maximum likelihood model comparison. The covariate model included the two variations of body weight and sex. Through the addition and subtraction of parameters, weight and gender had no significant effect on the alterations of PK parameters. Afterward, the random effects were introduced in the model, which notably reduced the coefficient of variation. Finally, the calculated values of the absorption rate constant, apparent distribution volume, and total systemic clearance were estimated to be 1.93/h, 11.16 L/kg, and 2.35 L/h/kg, respectively. The secondary parameters of the elimination rate constant, elimination half-life, and area under the concentration-time curve were calculated to be 0.20/h, 3.47 h, and 6.38 h.mg/L, respectively. This study supported a concise method for conducting PK studies in crustacean animals that facilitated the development of PK methodology in aquaculture.

Fasciola hepatica causes fasciolosis, a growing zoonotic disease that affects both livestock and humans worldwide. The main strategy to control fasciolosis in livestock animals, is based on drugs such as triclabendazole (TCBZ), albendazole (ABZ), clorsulon (CLOR), nitroxynil, closantel, and rafoxanide. Only TCBZ is available for F. hepatica control in human medicine and its resistance is growing. The use of drug combinations has been proposed as a strategy to delay it. This study compares the pharmacokinetics and flukicidal efficacy of ABZ + CLOR when administered together or separately in sheep infected with F. hepatica. Enhanced systemic exposure of the ABZ sulphoxide metabolite was observed after the co-administration ABZ + CLOR compared to the ABZ alone treatment. The CLOR disposition kinetics was not affected by its co-administration with ABZ. The flukicidal clinical efficacy was 85% (ABZ), 92% (CLOR) and 100% (ABZ + CLOR), respectively. The work described here contributes to the characterization of the disposition kinetics of both flukicidal molecules showing that the combined ABZ and CLOR therapy may enhance the efficacy against F. hepatica in sheep.

This work was aimed at investigating the pharmacokinetic changes after repeated administration of ketoprofen (3 mg/kg, IM, once a day for 5 days) to goats either alone or in combination with cefquinome (2 mg/kg, IM, once a day for 5 days). The study was carried out on six goats according to a balanced, open, two-phase, cross-pharmacokinetic design. The plasma ketoprofen concentrations were measured using HPLC-UV, and the pharmacokinetic data were estimated using a non-compartmental analysis. After the first dose of ketoprofen, the terminal elimination half-life (t_1/2ʎz), area under the plasma concentration–time curve (AUC_0–last), and peak plasma concentration (C_max) were 1.47 h, 12.23 h*μg/mL, and 6.06 μg/mL, respectively. The last dose of ketoprofen resulted in significant variations in t_1/2ʎz and AUC_0–last values compared to the first dose, but C_max was similar. Cefquinome administration caused significant differences in the t_1/2ʎz, AUC_0–last, and C_max of ketoprofen. There was no variation in T_max between the first and final doses or between treatment groups. The accumulation ratio of ketoprofen was 1.32 and 0.76 when used alone and in combination with cefquinome, respectively. Repeated administration of ketoprofen alone or with cefquinome altered its disposition; therefore, the efficacy of ketoprofen when used alone or in combination with cefquinome in goats should be determined, and the dosage regimen should be re-evaluated.

Achieving therapeutic plasma concentrations is essential for effective antimicrobial drug (AMD) treatment. Critical illness alters drug distribution and clearance, potentially impacting AMD effectiveness. We conducted a prospective observational study in 25 critically ill dogs to evaluate the pharmacokinetics (PK) of intravenous (IV) ampicillin/sulbactam and achievement of the efficacy target of ≥ 50% of the dosing interval with unbound plasma drug concentrations above the minimum inhibitory concentration (fT > MIC). All dogs received IV ampicillin/sulbactam from a commercial formulation at a dosage of 20 mg/kg ampicillin/10 mg/kg sulbactam. Plasma concentrations were measured using liquid chromatography–mass spectrometry. PK modeling determined best-fit compartmental models, and Monte Carlo simulations evaluated the probability of target attainment for bacterial MICs. A one-compartment model best described ampicillin PK, while a two-compartment model fit sulbactam. Monte Carlo simulations indicated a 90% probability that ampicillin at 20 mg/kg IV q8 h would achieve the Clinical and Laboratory Standards Institute (CLSI) veterinary breakpoint of 0.25 μg/mL for > 50% of the dosing interval. There was only a 10% probability of achieving the human breakpoint of 8 μg/mL. At 0.25 μg/mL, most Enterobacterales isolates would be resistant. The ampicillin/sulbactam dosage tested meets veterinary CLSI standards for ampicillin but might not effectively treat Enterobacterales infections in critically ill dogs.