[Biotransformation of diflucortolone valerate in the skin of rat, guinea pig and man (author's transl)].

The biotransformation of 6alpha,9-difluoro-11beta-hydroxy-16alpha-methyl-21-valeryloxy-1,4-pregnadiene-3,20-dione (diflucortolone valerate, DFV, Nerisona) was examined in vitro in the skin of rat and man and in vivo in the skin of guinea pigs. In the investigations with rat skin DFV in ethanolic solution (0.1 mumol) was added and the ester hydrolysis in buffer monitored in relation to the incubation time. In the experiments with guinea pigs and with human skin DFV was applied topically in the form of a 0.1% W/O emusion employing a dose of 6 mg/cm2 skin. After the substance which had not penetrated had been recovered by means of cotton wool and adhesive film at the end of the period of exposure the portions of skin were homogenized, extracted and the extracts separated by thin-layer chromatography. DFV is hydrolysed in the skin of rats and guinea pigs with a half-life of about 30-60 min to diflucortolone 6alpha,9-difluoro-11bets,21-dihydroxy-16alpha-methyl-1,4-pregnadiene-3,20-dione) and valeric acid. In excised human skin degradation of the ester proceeds much more slowly. Even 7 h p. appl. about 80-90% DFV and only 5-15% DF were identifiable in the skin extract. Despite the estremely low absorption rate the slow hydrolysis of DFV in human skin guarantees an adequate level of active ingredient in the skin over a long period.