Abstract
In vivo studies on the metabolism of trimethoprim have shown that N-oxidation to isomeric N-oxides occurs, with considerable inter-species variation in the proportion of each N-oxide excreted. No in vitro studies on the metabolism of trimethoprim have been reported to date. We now report a sensitive and specific HPLC method for the simultaneous determination of the isomeric N-oxides of trimethoprim. In vitro metabolic studies with hepatic microsomes from several animal species have been conducted. Optimum incubation conditions have been established and the use of potential metabolic inducers, activators and inhibitors has demonstrated that the N-oxidation of trimethoprim to its isomeric N-oxides is mediated via a cytochrome P450 dependent pathway.
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