DOSE-RESPONSE RELATIONS IN PHOTO-TOXICITY DUE TO 8-METHOXYPSORALEN AND UV-A IN MAN

[摘要] 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 (.+-. 24.2) and 311.4 (.+-. 55.6) ng/ml (mean and SE of the mean (SEM), respectively). The minimal phototoxic dose (MPD) of UVA 2 h after ingesting 8-MOP was determined in 6 volunteers for each of the 3 above-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.