Berezhkovskiy Leonid M
Genetech Inc, South San Francisco, California 94080, USA.
J Pharm Sci. 2009 Feb;98(2):748-62. doi: 10.1002/jps.21440.
The equation for the calculation of mean residence time of drug in plasma, t(p), is obtained. It is shown that the previously suggested calculation of t(p) considerably overestimates the true value in most cases. It is suggested that due to the possible initial (before establishing the uniform drug mixing in plasma) fast elimination of drug, the commonly calculated total body clearance (Cl = D/AUC) may substantially overestimate the clearance in the linear range of elimination of well-stirred drug. This would result in the high in vivo Cl values that are not supported by the in vitro studies of drug metabolism and stability in tissues. It is shown that the mean residence time of drug in the body, volumes of distribution, oral bioavailability and distribution clearance estimated with the account of initial drug distribution and elimination, may substantially deviate from the values obtained by the traditional calculations.
得出了计算药物在血浆中平均驻留时间t(p)的方程。结果表明，先前建议的t(p)计算方法在大多数情况下会显著高估真实值。研究表明，由于药物可能在初始阶段（在血浆中建立均匀药物混合之前）快速消除，通常计算的总体清除率（Cl = D/AUC）可能在药物线性消除范围内大幅高估清除率。这将导致体内Cl值过高，而这在药物代谢和组织稳定性的体外研究中并未得到支持。结果表明，考虑初始药物分布和消除后估算的药物在体内的平均驻留时间、分布容积、口服生物利用度和分布清除率，可能与传统计算得到的值有很大偏差。
