Extrahepatic Metabolism may Complicate the IVIVC in Rats

Title:Extrahepatic Metabolism may Complicate the IVIVC in Rats

Volume: 8 Issue: 1

Author(s): Massimiliano Fonsi

Affiliation:

Keywords: CYP1A1, extrahepatic metabolism, extrahepatic microsomes, human pharmacokinetic prediction, in vitro - in vivo correlation, liver microsomes, lung metabolism, lung microsomes, preclinical animal model, recombinant CYP450.

Abstract: As the liver is generally considered the organ most involved in metabolic transformations, metabolism in other organs is often overlooked and in vitro screening systems largely adopted in drug discovery are generally based on liver tissue fractions.

First pharmacokinetics of new chemical entities (NCEs) are initially based on preclinical species; rat is used in the majority of the cases to assess early in vitro-in vivo correlation (IVIVC). It is important, in this perspective, to address as early as possible the relevant differences between rat and human and the limits using pharmacokinetic studies in this species as a model for the human PK.

In this paper the author reports at least three clear examples in drug discovery where the use of hepatic in-vitro systems resulted in a very poor IVIVC due to relevant extrahepatic metabolism in rats.

Cite this article as:

Fonsi Massimiliano, Extrahepatic Metabolism may Complicate the IVIVC in Rats, Drug Metabolism Letters 2014; 8 (1) . https://dx.doi.org/10.2174/187231280801140929160226