Studies on 8-methoxypsoralen tolbutamide interactions in vitro and in vivo.

ABSTRACT

The present study aimed at characterizing the influence of tolbutamide on the distribution of 8-methoxypsoralen (8-MOP) in mouse serum and organs. Experiments performed in vitro clearly showed that tolbutamide causes competitive displacement of 8-MOP from its binding sites on human serum albumin. Similarly, the amount of labelled compound(s) bound in serum after oral administration of 3H-8-MOP to mice was significantly reduced when tolbutamide was given by the same route. The quantitative distribution of radioactivity from 3H-8-MOP in mouse tissues varied according to organ (liver, intestine, skin, etc.,), and was maximum in the organs of elimination. In all the organs studied, the administration of tolbutamide 2 hours after that of 3H-8-MOP caused a dose-dependent reduction of the radioactive compound(s) present in tissues, suggesting that tolbutamide may accelerate the excretion of 8-MOP and/or its metabolites from the body.