[Drug-drug interactions: predictive in vitro models of in vivo interactions. Round table no. 6.XV].
Liver drug metabolism is a major source of drug interactions. Three major human in vitro models are employed to detect drug interactions in the preclinical phases of drug development: recombinant enzymes, human liver microsomes and primary human hepatocyte cell cultures. Results obtained from these models may vary during the different phases of drug development. Identification of the metabolic pathways, enzymes involved in drug metabolism (mainly cytochrome P450s), enzyme induction or inhibition allow us to detect the major pharmacokinetic drug interactions which can occur in man and to identify specific populations at risk for such interactions. In vitro models are essential to decide if and which future drug interaction studies should be performed in man. However, the clinical relevance of the potential pharmacokinetic drug interactions detected by these in vitro models remains to be determined and confirmed by human studies.
Weber
F
F
Laboratoire Parke Davis, département de pharmacovigilance, Courbevoie, France.
Becquemont
L
L
D000818:Animals; D004347:Drug Interactions; D006801:Humans; D008099:Liver / Q000378:metabolism; D008954:Models, Biological; D010599:Pharmacokinetics; D011237:Predictive Value of Tests