Evaluation of the activity of P450 enzymes in rats: use of the single marker or combined drug administration.
OBJECTIVE
A "cocktail" of several substrates is frequently used to assess metabolic activity of multiple cytochrome P450 enzymes in one session. Some interactions among substrates can appear and may influence the rate of biotransformation of other ones. Our current work was aimed on the influence of tolbutamide on cytochrome P450-mediated metabolism of phenacetin and vice versa.


METHODS
In the presented work, the biotransformation rates of phenacetin and tolbutamide (markers of rat CYP1A2 and CYP2C6/11 metabolic activities, respectively) administered either separately or both simultaneously were compared. The model of isolated perfused rat liver was used.


RESULTS
Phenacetin had no significant effect on tolbutamide hydroxylation. Tolbutamide addition to the perfusion medium significantly increased the rate of O-deethylation of phenacetin.


CONCLUSIONS
Some differences in the rate of P450-mediated metabolism can be observed when comparing assessment using combination of two model substrates with the common way (single marker administration). Due to these differences, results obtained by the mentioned methodologies might not be fully comparable.
Jurica
Jan
J
Department of Pharmacology, Masaryk University, Brno, Czech Republic.
Kyr
Michal
M
McCaskey Hadasova
Eva
E
Tomandl
Josef
J
D000818:Animals; D001711:Biotransformation; D003577:Cytochrome P-450 Enzyme System / Q000737:chemistry / Q000378:metabolism*; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D010615:Phenacetin / Q000378:metabolism* / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors; D014044:Tolbutamide / Q000378:metabolism* / Q000494:pharmacology
D003577:Cytochrome P-450 Enzyme System; D014044:Tolbutamide; D010615:Phenacetin