The in vitro metabolism of oxodipine was studied with rat and human hepatic and intestinal microsomes. Rat liver, human liver and intestine were able to metabolize oxodipine in vitro to the main metabolites found in vivo, namely pyridine and deesterified derivatives; rat intestine did not produce any detectable metabolite. The Kms were found to be in the range of 30 to 60 microM. Human in vitro intestinal metabolism was negligible compared to that of liver and, taking into account the dose administered, it was predicted that the intestinal first-pass effect would also be negligible in vivo. The use of in vitro kinetic constants enabled us to evaluate the amount of oxodipine metabolized and to compare it to values found in vivo. Both results were on the same order of magnitude, indicating that it might be possible to evaluate the in vivo metabolism from in vitro data. Finally, we clearly showed, by substrate inhibition and immunoinhibition, that oxodipine was metabolized by the cytochrome P4503A subfamily both in intestine and in liver.