Mahmood Iftekhar
Office of Blood Review & Research, Center for Biologic Evaluation and Research, Food & Drug Administration, 1451 Rockville Pike, Maryland, USA.
J Pharm Sci. 2009 Jul;98(7):2472-93. doi: 10.1002/jps.21597.
Pharmacokinetic (PK) interspecies scaling is generally conducted using PK data from at least three animal species but three animal species may not be always available. In a recent manuscript, Tang et al. have described the methods to predict human drug clearance using one or two animal species. The authors claim that their proposed methods are better than the rule of exponents (ROE) which uses at least three animal species for the prediction of human drug clearance. A thorough examination of Tang et al.'s manuscript indicates that the data analysis may not be accurate. Considering that Tang et al.'s method may be of value, the objective of this study was to extend Tang et al.'s proposed methods for drugs given both intravenously and orally. The results of this study indicate that human drug clearance cannot be predicted with reasonable accuracy for most of the drugs by Tang et al.'s proposed methods and the accuracy of the prediction obtained from the ROE remains more accurate (based on average fold-error) than the one or two-species methods. This manuscript also clarifies some incorrect views regarding ROE presented by Tang et al. in their manuscript.
药代动力学（PK）种间缩放通常使用至少三种动物物种的PK数据进行，但并非总是能获得三种动物物种的数据。在最近的一篇手稿中，Tang等人描述了使用一两种动物物种预测人体药物清除率的方法。作者声称，他们提出的方法比使用至少三种动物物种预测人体药物清除率的指数规则（ROE）更好。对Tang等人手稿的全面审查表明，数据分析可能不准确。考虑到Tang等人的方法可能有价值，本研究的目的是扩展Tang等人提出的静脉内和口服给药药物的方法。本研究结果表明，对于大多数药物，Tang等人提出的方法无法以合理的准确性预测人体药物清除率，并且从ROE获得的预测准确性（基于平均倍数误差）仍然比一两种物种的方法更准确。本手稿还澄清了Tang等人在其手稿中提出的关于ROE的一些错误观点。
