Pharmacokinetic allometric scaling of coagulation factors and tissue-type plasminogen activators.
The objective of this study was to evaluate the predictive performance of pharmacokinetic interspecies scaling of coagulation factors and tissue-type plasminogen activators to predict clearance, volume of distribution at steady-state and half-life in humans from animal data. The human pharmacokinetic parameters were predicted using one, two or at least three animal species. The results of the study indicated that the pharmacokinetic parameters of coagulation factors and tissue-type plasminogen activators can be predicted with reasonable accuracy in humans when three or more animal species are available. Two-species scaling can also be performed, but the accuracy of predicted parameters is less than three-species scaling.
Mahmood
I
I
Office of Blood Review & Research (OBRR), Center for Biologic Evaluation and Research, Food & Drug Administration, Rockville Pike, MD, USA. iftekhar.mahmood@fda.hhs.gov
D000818:Animals; D001779:Blood Coagulation Factors / Q000493:pharmacokinetics*; D004353:Drug Evaluation, Preclinical / Q000379:methods; D006207:Half-Life; D006801:Humans; D008954:Models, Biological; D011237:Predictive Value of Tests; D013045:Species Specificity; D010959:Tissue Plasminogen Activator / Q000493:pharmacokinetics*
D001779:Blood Coagulation Factors; D010959:Tissue Plasminogen Activator