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Studies on 8-methoxypsoralen tolbutamide interactions. 2. Studies after U.V.-A irradiation in vitro and in vivo.

Previous studies had evidenced that tolbutamide has influence on the complex formation between 8-methoxypsoralen (8-MOP) and serum albumin, both in vitro and in vivo, partially displacing it from its binding site. We have now extended this research by studying competition under UV-A irradiation, thus approaching the conditions which occur during PUVA therapy more closely. Research was first carried out in vitro, studying tolbutamide competing with bound 8-MOP in human serum after irradiation with UV-A. From the data obtained, it appears that the displacement is not influenced to any significant extent by irradiation. Experiments were then carried out in vivo on mice treated with the two drugs and irradiated with UV-A in conditions analogous to those generally used for PUVA therapy; the amount of 8-MOP localized in blood serum and in various organs was then determined. Concerning distribution of 8-MOP, results confirmed what had been previously obtained; concerning irradiation, results showed that the effect on the 8-MOP displacement by tolbutamide was not statistically significative in the most organs considered. A slight difference in respect to the results obtained without irradiation was observed only in the cases of skin, eyes and ears.