Dose-response relations in phototoxicity due to 8-methoxypsoralen and UV-A in man

Serum levels and skin photosensitivity following different oral doses of 8-methoxypsoralen (8-MOP) were studied in 8 healthy volunteers. Two hours after ingestion of drug, serum levels of 8-MOP determined by high pressure liquid chromatography correlated well with oral dose. Serum concentrations after 8-MOP doses of 0.3, 0.6 and 0.9 mg/kg bodyweight were 25.9 (+/- 7.2), 148.9 (+/- 24.4) and 311.4 (+/- 55.6) ng/ml (mean and SEM) respectively. The minimal phototoxic dose (MPD) of UVA 2 hr after ingesting 8-MOP was determined in 6 volunteers for each of the 3 before-mentioned 8-MOP doses. The UV-A doses correlated inversely with the serum level for each individual (r = 0.92 +/- 0.02 SEM). For higher 8-MOP doses the numerical product of UV-A dose and 8-MOP serum concentration in each individual tended to be constant, indicating a reciprocal relationship between 8-MOP and UV-A doses in this interval. This did not hold true for the lowest 8-MOP-dose. These data confirm the relevance of using 8-MOP blood level determinations in monitoring psoralen-UV-A phototoxicity.