Prediction of human drug clearance from two species: a comparison of several allometric methods.
The objective of the study was to assess the degree of accuracy in human drug clearance prediction from two species using four different allometric approaches: simple allometry (SA), multiexponential allometry (ME), rule of exponents (ROE), and fixed exponents (FE) as suggested by Tang et al. There were 45 compounds in this analysis and the two species used were either rat-dog or rat-monkey. In addition, > or = 3 species scaling was also performed to evaluate the comparative accuracy in the prediction of human drug clearance between two or more than two-species scaling. The results of the study indicated that the two-species scaling with different methods provided different degrees of accuracy in the prediction of clearance. Prediction by a particular method was also species dependent. For example, a given drug with rat-dog scaling provided a reasonably accurate prediction of clearance whereas with rat-monkey scaling the prediction of clearance was highly erratic or vice versa. The results of the study indicated that the two-species scaling can be useful for prediction purposes but the prediction of clearance from > or = 3 species was far more accurate than two-species scaling.
Goteti
Kosalaram
K
Department of Drug Metabolism and Pharmacokinetics, AstraZeneca R&D Boston, 35 Gatehouse Drive, Waltham, Massachusetts 02451, USA. kosalaram.goteti@astrazeneca.com
Garner
C Edwin
CE
Mahmood
Iftekhar
I
D000465:Algorithms; D000818:Animals; D004285:Dogs; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D000882:Haplorhini; D006801:Humans; D008657:Metabolic Clearance Rate / Q000502:physiology*; D015233:Models, Statistical; D004364:Pharmaceutical Preparations / Q000378:metabolism*; D051381:Rats; D013045:Species Specificity
D004364:Pharmaceutical Preparations