INFLUENCE OF METOCLOPRAMIDE ON THE PHARMACOKINETICS OF 8-METHOXYPSORALEN

Background: Previous studies have shown important inter-and intraindiv idual variations in bioavailability of 8-methoxypsoralen (8-MOP) under the influence of factors that are not yet known with certainty. Howev er, they seem to be independent of age, sex and concomitant retinoid a dministration for RePUVA whereas the influence of diet remains controv ersial. Objective: The purpose of this study was to investigate a poss ible effect of metoclopramide on the bioavailability of 8-MOP since th ese drugs are frequently combined to prevent nausea, a common side eff ect of systemic 8-MOP. Methods: After a standard breakfast and the ing estion of 8-MOP plasma kinetics of 8-MOP were assessed in 6 healthy vo lunteers at 0, 1, 1.30, 1.45, 2, 2.15, 2.30, 3 and 4 h after drug inge stion. This procedure was repeated 3 weeks later by associating metocl opramide with 8-MOP. Plasma determinations of 8-MOP were performed usi ng high-pressure liquid chromatography. Results: Time and peak value o f maximum plasma 8-MOP concentration (T-max, C-max) ranged from 1 to 3 h and from 124 to 540 ng/ml, respectively. Individual values of the a rea under the curve of time-related 8-MOP concentration were between 2 84 and 1,158 ng.h/ml. Concomitant intake of 8-MOP with metoclopramide did not significantly influence these 3 pharmacokinetic values. Conclu sion: Our results confirm the important interindividual variability of the pharmacokinetics of 8-MOP. Associating 8-MOP with metoclopramide does not alter the pharmacokinetic values of 8-MOP and should not requ ire any change in PUVA treatment.