title: Controversy in the allometric application of fixed- versus varying-exponent models: a statistical and mathematical perspective.
abstract: This commentary is a reply to a recent article by Mahmood commenting on the authors' article on the use of fixed-exponent allometry in predicting human clearance. The commentary discusses eight issues that are related to criticisms made in Mahmood's article and examines the controversies (fixed-exponent vs. varying-exponent allometry) from the perspective of statistics and mathematics. The key conclusion is that any allometric method, which is to establish a power function based on a limited number of animal species and to extrapolate the resulting power function to human values (varying-exponent allometry), is infused with fundamental statistical errors.
authors.affiliation: Drug Metabolism and Pharmacokinetics, Merck Research Laboratory, Kenilworth, New Jersey 07033, USA. huadong.tang@spcorp.com
authors.forename: Huadong
authors.initials: H
authors.lastname: Tang
authors.forename: Azher
authors.initials: A
authors.lastname: Hussain
authors.forename: Mauricio
authors.initials: M
authors.lastname: Leal
authors.forename: Eric
authors.initials: E
authors.lastname: Fluhler
authors.forename: Michael
authors.initials: M
authors.lastname: Mayersohn
mesh_terms: D000818:Animals; D001682:Biological Availability; D001699:Biometry; D006801:Humans; D008657:Metabolic Clearance Rate; D008954:Models, Biological; D010599:Pharmacokinetics; D013045:Species Specificity