Pharmaceutical Research

, Volume 30, Issue 1, pp 1–15

A Physiologically Based Pharmacokinetic Model of the Minipig: Data Compilation and Model Implementation

Authors

    • F. Hoffmann-La Roche Ltd., Pharmaceuticals DivisionNon-Clinical Safety
  • Neil Parrott
    • F. Hoffmann-La Roche Ltd., Pharmaceuticals DivisionNon-Clinical Safety
Expert Review

DOI: 10.1007/s11095-012-0911-5

Cite this article as:
Suenderhauf, C. & Parrott, N. Pharm Res (2013) 30: 1. doi:10.1007/s11095-012-0911-5

Abstract

In today’s pharmaceutical research and development, physiologically-based pharmacokinetic (PBPK) modeling plays an important role in the design, evaluation and interpretation of pharmacokinetic, toxicokinetic and formulation studies. PBPK models incorporate in vitro physicochemical and biochemical data in a physiologically based model framework to simulate in vivo exposure. The comparison of simulated concentrations to those measured in in vivo studies can be used to gain insights into compound behavior and to inform PBPK based human pharmacokinetic predictions. The Göttingen minipig is gaining importance as a large animal model in pharmaceutical research due to its physiological and anatomical similarities to human and is increasingly replacing dog and non-human primate in preclinical studies. However, no PBPK model for minipig has yet been published. This review discusses the information available to establish the physiological database for this species and highlights the gaps in current knowledge. A preliminary PBPK model is created from this database and simulations for two drugs dosed both intravenously and orally are compared to measured plasma concentrations. Results support the validity of the model with simulated plasma concentrations within the range of the observations. In conclusion, the model will need to be refined as additional physiological data become available, but it can already provide useful simulations to assist pharmaceutical research and development in the minipig.

KEY WORDS

absorption modelingdistributioneliminationintestinal absorptionmetabolismminipigphysiologically based pharmacokinetic modelingpig

Abbreviations

ACAT

Advanced Compartmental Absorption and Transit

BCS

Biopharmaceutics Classification System

CO

cardiac output

CYP

cytochrome P450

Fabs

fraction of dose absorbed

GFR

glomerular filtration rate

GI

gastrointestinal

PBPK

physiologically based pharmacokinetic

PK

pharmacokinetics

SEF

surface area enhancement factor

Supplementary material

11095_2012_911_MOESM1_ESM.doc (110 kb)
ESM 1(DOC 109 kb)

Copyright information

© Springer Science+Business Media New York 2012