The Skin Concentration and Minimal Phototoxic Dose Following Administration of Phototoxic Drugs as a Function of Time Yoon-Kee Park, M.D., Moo Yon Cho, M.D., Saung Kyung Hann, M.D., Sungbin im, M.D. Department of Dermatology Yonsei Univeraity College of Medicine, Seoul, Korea Psoralen photochemotherapy(PUVA) is defined as a treatment that depends on the interaction of a photosensitizing substance, psoralen, and long wave jltraviolet(UVA) radiation that results in therapeutically beneficial effects. The rationale of its use is to clear skin disease by repeated controlled phototoxic reactions. The efficacy of PUVA depends on the drug, the UVA dose and wave length, the individual sensitivity to the phototoxic reaction and on the disease to be treated. However, the major factor is the amount of psoralen at the site of photochemical reaction in skin. Daspite the extensive experiences which have now accumulated in the use of PUVA, the relationship between the therapeutic response and phototoxicity as it occurs in normal skin is not established. Comparative data on different psoralen molecules and their skin sensitizing ability are required. From studies on the skin concentration using HPLC and minimal phototoxic dose following oral administration, intraperitoneal administration, a bath of phototoxic drugs as a function of time in guinea pigs, the following results are obtained. 1. The skin concentration of phototoxic drugs after oral administration peaked at 1.5 hours, and the concentration of 8-methoxypsoralen(8-MOP) was 3.7 times greater than that of 5-methoxypsoralen(5-MOP). The skin concetration of 4,5,8-trimethylpsoralen(TMP) was not detected in this study(limit of sensitivity 5ng/g). 2. The skin conentration of phototoxic drugs after intraperitoneal administration peaked at 30 minutes, and the concentration of 8-MOP was slightly greater than that of 5-MOP. The skin concentration of TMP was not detected in this study(limit of sensitivity 5ng/g). 3. The skin concentration of phototoxic drugs after bathing peaked immediately after bathing, and the skin concentrations of phototoxic drugs after bathing decreased in the order of 5-MOP, TMP, and 8-MOP. 4. The minimal phototoxic dose of phototoxic drugs after oral administration was lowest at 1.5 hours, and the minimal phototoxic dose of 8-MOP was 8 times less than 5-MOP, 24 times less than TMP. The phototoxicity of 8-Mop after oral administration was strongest. The time of lowest phototoxic dose and highest skin concentration was the same. 5. The minimal phototoxic dose of phototoxic drugs after intraperitoneal administration was lowest at 30 minutes, and the minimal phototoxic dose of 8-MOP was 1.3 times less than 5-MOP, 5.7 times less than TMP. The phototoxicity of 8-MOP after intraperitoneal administration was strongest. The time of lowest phototoxic dose and highest skin concentration was same. 6. The minimal phototoxic dose of phototoxic drugs after bathing was lowest at 15 minutes. The minimal phototoxic dose of 8-MOP was not significantly different but was significantly greater than that of 5-MOP.