Utility of Göttingen minipigs for the prediction of human pharmacokinetic profiles after intravenous drug administration

Abstract Gottingen minipigs are increasingly used to evaluate the pharmacokinetic (PK) profiles of drug candidates. However, their accuracy in predicting human PK parameters is unclear. In this study, we investigated the utility of Gottingen minipigs for predicting human PK profiles. We evaluated the PK parameters of 30 compounds with diverse metabolic pathways after intravenous administration in minipigs. Human total clearance (CLtotal) was corrected using the blood to plasma ratio, and the volume of distribution at steady state (Vd(ss)) was corrected with plasma unbound fraction (fup). CLtotal and Vd(ss) were predicted using single-species allometric scaling using data from minipigs and other reported animal models (monkeys, human liver chimeric mice, and rats). The predicted values were compared with actual values reported in humans. Gottingen minipig were superior to rats because of their better predictability of Vd(ss) and CLtotal, as represented by lower absolute average fold error values. However, their predictability for Vd(ss) was inferior to monkey and human liver chimeric mice. Prediction of CLtotal from blood-based minipig data showed excellent correlation with human data, and comparable predictability with monkey and human liver chimeric mice. Thus, Gottingen minipigs can be used as an optional model for preclinical pharmaceutical research for predicting human CLtotal.