Pharmacokinetics and pharmacodynamics of psoralens after oral administration: considerations and conclusions.

We discovered a strong but saturable first-pass effect after oral administration of psoralens by using different doses and simultaneous or timed application of stable isotopes. Therefore, small variations of dose, disintegration of drug, and amount and rate of absorption gave rise to great differences in plasma levels and therapeutic efficacy. For practical therapy, the following conclusions can be drawn: 1) Galenical forms of psoralens should ensure a quick and highly reproducible absorption. 2) In the event that inefficacy has been detected, plasma levels should be determined, and the psoralen dosage should be increased rather than the irradiation doses in most instances. 3) For oral psoralen and 320- to 400-nm UV (UVA) treatment, a combination of 5-methoxypsoralen (5-MOP) and 8-MOP (with a lower dose and either administered 30 minutes later than the 5-MOP or in a drug product with quick release of 5-MOP and quick but delayed release of 8-MOP) results in much higher efficacy and reproducibility. Therefore, compared with the single drug, in the combination, dose of drug and the amount of irradiation can be reduced considerably which may result in increased safety. 4) Plasma levels after oral administration of dissolved 4,5',8-trimethylpsoralen are low, but phototoxicity is comparable to that of the 5-MOP and 8-MOP.