Patel B A, Boudinot F D, Schinazi R F, Gallo J M, Chu C K
Department of Pharmaceutics, College of Pharmacy, University of Georgia, Athens 30602.
J Pharmacobiodyn. 1990 Mar;13(3):206-11. doi: 10.1248/bpb1978.13.206.
Interspecies variation in drug disposition can be considered to be a function of species body weight. Therefore, it is possible to establish allometric relationships between pharmacokinetic parameters and species body weight. Interspecies scaling of pharmacokinetic data yielded from laboratory animals can often provide reliable predictions of pharmacokinetic parameters and drug disposition in humans. Significant correlations between 3'-azido-3'-deoxythymidine (AZT) pharmacokinetic parameters (total clearance, renal clearance, nonrenal clearance and steady-state volume of distribution) from mice, rats, dogs, monkeys and humans and body weight were found. Plasma AZT concentration versus chronological time profiles were markedly different for each species. However, when chronological time was converted to pharmacokinetic (physiologic) time these profiles were superimposible. These results demonstrate that interspecies pharmacokinetic scaling can be used to estimate plasma AZT concentrations in humans and can be used to design initial dosage regimens.
药物处置的种间差异可被视为物种体重的函数。因此，有可能建立药代动力学参数与物种体重之间的异速生长关系。从实验动物获得的药代动力学数据的种间缩放通常可以为人体药代动力学参数和药物处置提供可靠的预测。发现小鼠、大鼠、狗、猴子和人类的3'-叠氮-3'-脱氧胸苷（AZT）药代动力学参数（总清除率、肾清除率、非肾清除率和稳态分布容积）与体重之间存在显著相关性。每个物种的血浆AZT浓度随时间变化的曲线明显不同。然而，当将时间转换为药代动力学（生理）时间时，这些曲线是可叠加的。这些结果表明，种间药代动力学缩放可用于估计人体血浆AZT浓度，并可用于设计初始给药方案。
