Usefulness of minipigs for predicting human pharmacokinetics: Prediction of distribution volume and plasma clearance

Drug Metabolism and Pharmacokinetics
Hiromichi YoshimatsuShinji Yamashita

Abstract

In this study, advantages of minipigs to use in preclinical study for new drug development were evaluated in terms of prediction of human pharmacokinetic (PK) parameters of various drugs. Fourteen model drugs having diverse physicochemical properties were selected and intravenously administered to mice, rats and minipigs to obtain their PK parameters. The human volume of distribution (Vd) and clearance (CL) of model drugs were predicted from PK parameters in each animal species. When Vd of 14 drugs in each species were directly compared with those in humans, minipigs showed the highest correlation. Correction of Vd with an unbound fraction of drugs in tissues further improved the correlation. Allometric scaling that included minipig data resulted in high accuracy in the prediction of human Vd, clearly indicating an importance of minipig data. Minipigs also showed the high predictability of human CL. The prediction of human CL by allometric scaling showed a high accuracy when the data of minipigs were included. In conclusion, potential advantages of minipigs for predicting human Vd and CL were clearly demonstrated. Reliable prediction of human PK from data of minipigs appears to be possible in preclinical PK study, without relyi...Continue Reading

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Citations

Dec 16, 2016·Biopharmaceutics & Drug Disposition·Jean-Marie NicolasAnna-Lena Ungell
Mar 11, 2017·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·Rachel D CrouchJ Scott Daniels
Sep 2, 2018·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Huadong Tang, Michael Mayersohn
Jul 4, 2020·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Takayuki TaguchiYukio Kato
Jul 19, 2019·Frontiers in Pharmacology·Joske MillecamMathias Devreese
May 6, 2017·The AAPS Journal·David J WilkinsonMichael B Otteneder
Aug 1, 2021·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·Daigo AsanoKouichi Yoshinari
Aug 25, 2021·Translational Research : the Journal of Laboratory and Clinical Medicine·Karen-Margrethe PedersenHanne Hoffmann Frølund Refsgaard
Sep 20, 2020·International Journal of Pharmaceutics·Indushekhar PersaudSwamy Yeleswaram

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