College of Animal Science and Technology, Henan University of Science and Technology, Luoyang, China.
J Vet Pharmacol Ther. 2022 May;45(3):311-319. doi: 10.1111/jvp.13049. Epub 2022 Mar 4.
A flow-limited physiologically based pharmacokinetic (PBPK) model consisting of seven compartments was established for orbifloxacin in crucian carp to predict drug concentrations after intravenous or intramuscular injections. Physiological and anatomical parameters, including tissue weights and blood flow through different tissues, were obtained from previous literature. The tissue/plasma partition coefficients for orbifloxacin were calculated using the area method or parameter optimization. In addition, their values were 0.9326, 1.1204, 1.1644, 1.3514, and 2.0057 in the liver, skin, muscle, kidney, and the rest of the body compartment, respectively. Based on the current PBPK model, orbifloxacin concentrations were predicted and compared with those previously reported for further validation. In addition, the mean absolute percentage error (MAPE) values were also calculated, with values ranging from 10.21% in plasma to 42.37% in kidneys, indicating acceptable predictions for all tissues and plasma. A local sensitivity analysis was performed, which showed that the parameters related to elimination and distribution were most influential on orbifloxacin concentrations in muscle. This model was finally used to predict plasma and tissue concentrations after multiple intramuscular dosing. The current PBPK model provided a valuable tool for predicting the tissue residues of orbifloxacin in crucian carp following intramuscular injection.
建立了一个包含七个隔室的、基于生理的药代动力学（PBPK）模型，用于预测鲫鱼静脉或肌肉注射后氧氟沙星的药物浓度。生理和解剖参数，包括组织重量和不同组织中的血流，从以前的文献中获得。使用面积法或参数优化计算氧氟沙星的组织/血浆分配系数。此外，其值分别为 0.9326、1.1204、1.1644、1.3514 和 2.0057，分别在肝脏、皮肤、肌肉、肾脏和身体其他部位。基于当前的 PBPK 模型，预测了氧氟沙星的浓度，并与以前报道的浓度进行了比较，以进一步验证。此外，还计算了平均绝对百分比误差（MAPE）值，范围从血浆中的 10.21%到肾脏中的 42.37%，表明所有组织和血浆的预测都可以接受。进行了局部敏感性分析，结果表明，与消除和分布相关的参数对肌肉中氧氟沙星浓度的影响最大。最后，该模型用于预测多次肌肉注射后的血浆和组织浓度。该 PBPK 模型为预测鲫鱼肌肉注射氧氟沙星后的组织残留提供了一种有价值的工具。
