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  • Title: Predictability of the in vivo metabolism of verapamil from in vitro data: contribution of individual metabolic pathways and stereoselective aspects.
    Author: Kroemer HK, Echizen H, Heidemann H, Eichelbaum M.
    Journal: J Pharmacol Exp Ther; 1992 Mar; 260(3):1052-7. PubMed ID: 1545377.
    Abstract:
    In vitro studies of drug metabolism with human liver microsomes can be performed in the early stages of drug development. Such experiments may reflect the in vivo metabolism of drugs in humans and thus allow for a prediction of drug disposition before the compound is administered to humans. We tested this hypothesis for the example of verapamil, which is a calcium channel blocker that undergoes extensive metabolism. Moreover, the drug is administered as a racemate, and stereoselective first-pass metabolism favoring the extraction of the more potent S-verapamil is observed after p.o. administration. To evaluate the in vitro metabolism, microsomes prepared from 10 human livers were incubated with both S- and R-verapamil.(ABSTRACT TRUNCATED AT 250 WORDS)
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