ABSTRACT
A [cocktail] of several probe drugs is often used to evaluate metabolic activity of multiple cytochrome P450 enzymes in one session. Some interactions among probe drugs can appear and may impact the rate of biotransformation of other ones. Our presented work was aimed on the influence of bupropion on cytochrome P450-mediated metabolism of tolbutamide. The biotransformation rates of tolbutamide administered either separately or in combined with bupropion were compared in this study. The results revealed that bupropion had no significant effect on tolbutamide hydroxylation. Thus, due to stability in cytochrome P450 enzyme metabolic activity in the case of combining of two model probe drugs the procedure can show to no extent differential results comparing to the single-marker use
ABSTRACT
A "cocktail"of numerous probe drugs to assess the metabolic activity of the corresponding cytochrome P450 enzymes requires that there is no problem of interaction among them. Some interactions among probe drugs can appear and may affect the rate of biotransformation of other ones. To develop a useful "cocktail" of probe drugs, our presented work was aimed on the influence of tolbutamide on cytochrome P450-mediated metabolism of bupropion. The biotransformation rates of bupropion administered either separately or in combined with tolbutamide were compared in this new study. The results revealed that tolbutamide had significantly decreased the rate of bupropion hydroxylation. Thus, due to shift in cytochrome P450 enzyme metabolic activity some extent differential results in the rate of P450-mediated metabolism can be observed when comparing assessment using combination of two model drugs with the common way [single marker use]