The effect of psoralens on hepatic and cutaneous drug metabolizing enzymes and cytochrome P-450.

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.