Journal of veterinary pharmacology and therapeutics最新文献

The objective of this study was to investigate the population pharmacokinetics of sarafloxacin following a single oral administration at a dose of 20 mg/kg body weight (BW) in Yellow River carp (Cyprinus carpio haematopterus) reared at 24°C, and to provide a scientific basis for its rational use in aquaculture. Blood samples were collected from the tail vein of six fish at each predetermined time point: 0.25, 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 36, 46, 48, 92, 96, 120, and 144 h post-administration, using a sparse sampling design. Blood was collected only four times per fish, and six fish were sampled at each time point. Plasma concentrations of sarafloxacin were measured using high-performance liquid chromatography (HPLC), and the drug remained quantifiable in plasma up to 120 h post-administration. Population pharmacokinetic modeling was conducted using nonlinear mixed-effects modeling to characterize both the typical population parameters (fixed effects) and inter-individual variability (random effects). Covariate and covariance models were incorporated to account for variability and improve model predictability under sparse sampling conditions. The final population model estimated typical values (tv) and inter-individual coefficients of variation (CV%) for the absorption rate constant (tvK_a), apparent volume of distribution (tvV), and clearance (tvCL) as 14.889 h⁻¹ (CV: 3.04%), 31.573 L/kg (CV: 0.39%), and 2.885 L/h/kg (CV: 0.38%), respectively. Based on the calculated AUC/MIC or C_max/MIC ratios, the current oral dosing regimen of 20 mg/kg BW appears to be effective against pathogens with MIC values below 0.05 μg/mL.

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.