Comparison of the "cocktail approach" with single marker administration in evaluating the activity of P450 enzymes in rats

Authors

JUŘICA Jan TOMANDL Josef KÝR Michal MCCASKEY HADAŠOVÁ Eva

Year of publication 2009
Type Article in Periodical
Magazine / Source Interdisciplinary Toxicology
MU Faculty or unit

Faculty of Medicine

Citation
Field Pharmacology and pharmaceutical chemistry
Description The activity of cytochrome P450 enzymes (CYP) is most often measured using selective substrate of distinct P450 enzyme. Moreover, there are often used more substrates together, so as the activity of multiple P450 enzymes could be measured simultaneously. Despite of the potential risk of interactions and side effects of these markers used in vivo, such a "cocktail" approach brings another question - can one marker influence the rate of biotransformation of another one? The aim of the present work was to compare biotransformation rate of phenacetin and tolbutamide (markers of CYP1A2 and CYP2C6/11 activity) administered either separately or both simultaneously.Our results suggest that phenacetin addition had no significant effect on tolbutamide hydroxylation. On the other hand, tolbutamide addition to the perfusion medium significantly increased the rate of O-deethylation of phenacetin.
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