title: A unified strategy in selection of the best allometric scaling methods to predict human clearance based on drug disposition pathway.
abstract: 1. It is critical to develop a unified strategy to select the best allometric scaling (AS) method for a given group of drugs. 2. A total of 446 drugs with known human CLiv, clear disposition pathway and animal (rat, dog, monkey) CLivwere analyzed. All drugs were stratified based on their disposition pathway, liver extraction ratio (ERH) and ratios of unbound clearance to renal glomerular filtration rate (RGFR). Up to 22 AS methods were applied and compared in prediction of human CLivto each group of drugs. 3. AS methods that give the best prediction of human CLiv, were identified for drugs primarily eliminated through liver with a fraction of renal elimination (frenal) within 0.3-0.5 or ERH> 0.3, where human CLivof more than 80% or 90% drugs could be accurately (within 2- or 3-fold error) predicted. For drugs with ERH< 0.3, acceptable accuracy could be achieved by a two species method TSR,Dresulting more than 60% or 75% drugs were predicted within 2- or 3-fold error. 4. By stratified analysis of drugs, according to their disposition pathway and organ extraction ratio, a unified strategy was developed to select the best AS method in prediction of human CLiv.
authors.affiliation: a Clinical Pharmacology Research Center, Peking Union Medical College Hospital and Chinese Academy of Medical Sciences , Beijing , China.
authors.forename: Dongyang
authors.initials: D
authors.lastname: Liu
authors.affiliation: a Clinical Pharmacology Research Center, Peking Union Medical College Hospital and Chinese Academy of Medical Sciences , Beijing , China.
authors.forename: Hanlin
authors.initials: H
authors.lastname: Song
authors.affiliation: a Clinical Pharmacology Research Center, Peking Union Medical College Hospital and Chinese Academy of Medical Sciences , Beijing , China.
authors.forename: Ling
authors.initials: L
authors.lastname: Song
authors.affiliation: a Clinical Pharmacology Research Center, Peking Union Medical College Hospital and Chinese Academy of Medical Sciences , Beijing , China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Liu
authors.affiliation: b Division of Pharmacotherapy and Experimental Therapeutics , Eshelman School of Pharmacy, University of North Carolina at Chapel Hill , Chapel Hill, North Carolina , USA.
authors.forename: Yanguang
authors.initials: Y
authors.lastname: Cao
authors.affiliation: a Clinical Pharmacology Research Center, Peking Union Medical College Hospital and Chinese Academy of Medical Sciences , Beijing , China.
authors.forename: Ji
authors.initials: J
authors.lastname: Jiang
authors.affiliation: a Clinical Pharmacology Research Center, Peking Union Medical College Hospital and Chinese Academy of Medical Sciences , Beijing , China.
authors.forename: Pei
authors.initials: P
authors.lastname: Hu
mesh_terms: D000818:Animals; D004285:Dogs; D005919:Glomerular Filtration Rate; D000882:Haplorhini; D006801:Humans; D008657:Metabolic Clearance Rate; D008954:Models, Biological; D004364:Pharmaceutical Preparations / Q000378:metabolism*; D010599:Pharmacokinetics; D051381:Rats; D013045:Species Specificity
chemical_list: D004364:Pharmaceutical Preparations
keywords: Allometric scaling; disposition pathway; human clearance; prediction