8-Methoxypsoralen plasma levels and phototoxic effect

In 8 normal volunteers, the minimal phototoxic dose was determined at 15 min intervals up to 60 min and thereafter every 30 min up to 4 h; 8-methoxypsoralen (8-MOP) was administered as a solution and small additional doses were given during the course of the experiment, so that a more or less predictable and stable plasma concentration was obtained and maintained for about 2 h. Three of the subjects absorbed 8-MOP very rapidly, already reaching plasma concentrations above 200 ng/ml after 15 min; in the other 5, absorption was slower and comparable levels were achieved only after 30 to 90 min. In the fastest absorbers, there was a 15 to 30 min lag between reaching a high plasma level and a low MPD. In the other cases, such a delay was not seen. This suggests that the time to reach peak concentration in the skin is not influenced by changes in absorption rate: simulations based on the classical plasma concentration equations for a two-compartmental model also show this. Afterwards, the skin sensitivity decreased in most cases parallel to the plasma concentrations.