title: Role of fixed coefficients and exponents in the prediction of human drug clearance: how accurate are the predictions from one or two species?
abstract: 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.
authors.affiliation: Office of Blood Review & Research, Center for Biologic Evaluation and Research, Food & Drug Administration, 1451 Rockville Pike, Maryland, USA. iftekhar.mahmood@fda.hhs.gov
authors.forename: Iftekhar
authors.initials: I
authors.lastname: Mahmood
mesh_terms: D000818:Animals; D001682:Biological Availability; D001699:Biometry; D004285:Dogs; D000882:Haplorhini; D006801:Humans; D008657:Metabolic Clearance Rate; D051379:Mice; D008954:Models, Biological; D010599:Pharmacokinetics; D051381:Rats