Influence of metoclopramide on the pharmacokinetics of 8-methoxypsoralen.

BACKGROUND

Previous studies have shown important inter- and intraindividual variations in bioavailability of 8-methoxypsoralen (8-MOP) under the influence of factors that are not yet known with certainty. However, they seem to be independent of age, sex and concomitant retinoid administration for RePUVA whereas the influence of diet remains controversial.

OBJECTIVE

The purpose of this study was to investigate a possible effect of metoclopramide on the bioavailability of 8-MOP since these drugs are frequently combined to prevent nausea, a common side effect of systemic 8-MOP.

METHODS

After a standard breakfast and the ingestion of 8-MOP plasma kinetics of 8-MOP were assessed in 6 healthy volunteers at 0, 1, 1.30, 1.45, 2, 2.15, 2.30, 3 and 4 h after drug ingestion. This procedure was repeated 3 weeks later by associating metoclopramide with 8-MOP. Plasma determinations of 8-MOP were performed using high-pressure liquid chromatography.

RESULTS

Time and peak value of maximum plasma 8-MOP concentrations (Tmax, Cmax) ranged from 1 to 3 h and from 124 to 540 ng/ml, respectively. Individual values of the area under the curve of time-related 8-MOP concentration were between 284 and 1,158 ng-h/ml. Concomitant intake of 8-MOP with metoclopramide did not significantly influence these 3 pharmacokinetic values.

CONCLUSIONS

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 require any change in PUVA treatment.