Song Zhe-Wen, Yang Fang, Dai Yan, Zhang Chao-Shuo, Shao Hao-Tian, Wang Han, Ma Kai-Li, Li Ze-En, Yang Fan
Department of Veterinary Pharmacology, College of Animal Science and Technology, Henan University of Science and Technology, Luoyang, China.
Front Vet Sci. 2022 Apr 6;9:868966. doi: 10.3389/fvets.2022.868966. eCollection 2022.
This study aimed to determine the population pharmacokinetics of danofloxacin in healthy Yellow River carp () after single oral administration at 10 mg/kg body weight (BW). A sparse sampling was applied in this study and plasma samples were randomly collected from the tail veins of six carp at 0.25, 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 36, 48, 72, 96, 120 and 144 h after administration. A maximum of four plasma samples was collected from each carp. Then the concentrations of danofloxacin in plasma samples were determined through an HPLC method. Danofloxacin could be quantified in plasma up to 144 h after administration. The corresponding population pharmacokinetic modeling was developed according to the non-linear mixed effect method, including covariate and covariance models to explain some variations from unknown sources and improve the prediction ability. On the premise of sparse sampling, the typical values of the population (fixed effect) and inter-individual variation (random effect) were described by the current population pharmacokinetic model. The estimated typical values and coefficient of variation between individuals (CV%) of absorption rate constant (tvKa), apparent distribution volume (tvV) and clearance (tvCL) were 2.48 h and 0.203%, 47.8 L/kg and 8.40%, 0.694 L/h/kg and 4.35%, respectively. The current danofloxacin oral dosing (10 mg/kg BW) can provide suitable plasma concentrations to inhibit those pathogens with MIC values below 0.016 μg/ml based on the calculated PK/PD indices of AUC/MIC or C/MIC. Further studies are still needed to determine the and antibacterial efficacy of danofloxacin against pathogens isolated from Yellow River carp and finally draw a reasonable dosing regimen.
本研究旨在确定健康黄河鲤单次口服10 mg/kg体重的达氟沙星后的群体药代动力学。本研究采用稀疏采样法，在给药后0.25、0.5、1、2、4、6、8、12、16、24、36、48、72、96、120和144小时从6尾鲤鱼的尾静脉随机采集血浆样本。每尾鲤鱼最多采集4份血浆样本。然后通过高效液相色谱法测定血浆样本中达氟沙星的浓度。给药后144小时内血浆中均可检测到达氟沙星。根据非线性混合效应法建立相应的群体药代动力学模型，包括协变量和协方差模型，以解释未知来源的一些变异并提高预测能力。在稀疏采样的前提下，当前的群体药代动力学模型描述了群体的典型值（固定效应）和个体间变异（随机效应）。吸收速率常数（tvKa）、表观分布容积（tvV）和清除率（tvCL）的估计典型值和个体间变异系数（CV%）分别为2.48小时和0.203%、47.8 L/kg和8.40%、0.694 L/h/kg和4.35%。根据计算的AUC/MIC或C/MIC的PK/PD指数，当前达氟沙星口服剂量（10 mg/kg体重）可提供合适的血浆浓度以抑制MIC值低于0.016 μg/ml的病原体。仍需进一步研究以确定达氟沙星对从黄河鲤分离的病原体的抗菌疗效，并最终制定合理的给药方案。
