Journal of veterinary pharmacology and therapeutics最新文献

This study investigated the pharmacokinetics of enrofloxacin (ENR) and its primary metabolite, ciprofloxacin (CIP), in black rockfish (Sebastes schlegelii) following a single oral administration of ENR (10 mg/kg) under two water temperature conditions (13°C and 22°C). Serum samples were collected up to 168 h post-dosing and analyzed using a validated HPLC-MS/MS method. Contrary to conventional expectations, ENR absorption was delayed and elimination was slower at 22°C compared to 13°C, while the plasma concentrations of CIP were higher at the elevated temperature. The elimination half-life of ENR increased from 27.38 h at 13°C to 42.01 h at 22°C, despite enhanced hepatic metabolism. These findings suggest that the primary route of ENR elimination may shift from passive diffusion via the gills at lower temperatures to hepatic metabolism at higher temperatures, likely due to functional impairment of the gill tissues under thermal stress. Notably, the AUC values of ENR remained comparable between the two groups, indicating consistent drug exposure despite differing pharmacokinetic dynamics. PK/PD analysis revealed that single-dose administration may not achieve optimal therapeutic indices (AUC_0-24h/MIC ≥ 125, C_max/MIC ≥ 10) against certain bacterial pathogens, underscoring the need for repeated dosing. Overall, this study provides novel insights into the temperature-modulated pharmacokinetics of ENR and highlights the importance of temperature-specific dosing strategies for effective antibiotic therapy in aquaculture species like black rockfish.

Anthelmintic resistance is a major welfare issue in goats, and the efficacy of anthelmintic drugs lies in judicious use. Recently, an injectable combination (levamisole–doramectin) product labeled for cattle became available. This study's goal was to compare the levamisole pharmacokinetic parameters of this new combination drug to a commercially available oral levamisole formulation in goats. Six adult goats received a 9 mg/kg dose subcutaneously of the combination product. Blood samples were collected at 14 time points over 48 h. After a 14-day washout period, the same goats were given 12 mg/kg of oral levamisole and sampled following the same time points. Levamisole concentrations were measured via liquid chromatography. A non-compartmental analysis was used to generate pharmacokinetic (PK) parameters for both formulations. After one subcutaneous (SC) injection, the maximum plasma concentration (C_max), time to C_max (T_max), area under the curve (AUC), and elimination half-life (T_1/2) were 468.57 ± 151.12 ng/mL, 2.24 ± 1.58 h, 3206.42 ± 1189.73 h ng/mL, and 2.36 ± 2.07 h, respectively. After a single oral administration, C_max, T_max, AUC, and T_1/2 were 573.21 ± 149.01 ng/mL, 0.5 ± 0.41 h, 2995.47 ± 2203.93 h ng/mL, and 3.74 ± 2.19 h, respectively. Fecal samples taken before and after subcutaneous administration had an average egg count reduction of 61.97% (p = 0.0625). The relative bioavailability of the SC injection was 185%. Considering bioavailability and egg count reduction, the combination product may be considered for parasite management; however, a field trial is needed to determine its efficacy and other pharmacodynamic parameters.

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.