The Effect of Psoralens on Hepatic and Cutaneous Drug Metabolizing Enzymes and Cytochrome P-450

Abstract

Psoralens are tricyclic furocoumarins with potent photosensitizing properties in the skin and are now widely used in the treatment of several dermatologic diseases. In this study the effect of 3 different psoralens 8-methoxypsoralen (8-MOP), 4,5',8-trimethylpsoralen (TMP) and isopsoralen on hepatic microsomal drug-metabolizing enzymes and cytochrome P-450 has been assessed in mice and rats. 8-MOP administered orally to CD-1 mice daily for 6 days caused 2-3 fold increases in hepatic aryl hydrocarbon hydroxylase (AHH), ethylmorphine N-demethylase and cytochrome P-450. The absorbance maximum of the induced cytochrome was at 450 nm. Aniline hydroxylase activity was unchanged. Chronic administration of 8-MOP to hairless mice caused significant enhancement of hepatic ethylmorphine N-demethylase and cytochrome P-450 but had no effect on AHH; whereas chronically administered TMP had no significant effect on any of these parameters. Isopsoralen and TMP administered orally to CD-1 mice daily for 6 days had no effect on any of these liver enzymes or on hepatic P-450. 8-MOP administered daily for 6 days to rats caused a greater than 4-fold enhancement of AHH and greater than 2-fold enhancement of ethylmorphine N-demethylase and cytochrome P-450. These studies indicate that orally administered 8-MOP induces hepatic drug-metabolizing enzymes and cytochrome P-450 to a lesser extent than do the barbituates and suggest that this drug could influence the rate of biotransformation of concomitantly administered drugs in patients undergoing PUVA therapy.