[Percutaneous absorption of diflucortolone valerate in guinea pigs and man (author's transl)].

Percutaneous absorption of 6alpha,9-difluoro-11beta-hydroxy-16alpha-methyl-21-valeryloxy-1,4-pregnadiene-3,20-dione (difucortolone valerate, Nerisona) as dependent on the base, the concentration in the base and the condition of the skin was investigated in man and in guinea pigs. In addition the distribution of the corticoid in the stratum corneum, epidermis and corium was determined by stripping the skin and by horizontal thin-section technique. 2. In man diflucortolone valerate from all of the formulations tested (0.1 and 0.3% cream, ointment and fatty ointment) was only absorbed to a slight extent by both the intact and the stripped areas of skin on the subjects' backs. In the case of the 0.1% formulations a total of about 0.2% of the dose was absorbed within 4 h via intact skin and about 0.4% via the stripped skin. After application of the 0.3% formulations the percutaneous absorption from the ointment, fatty ointment and cream were examined separately. This revealed percutaneous absorption within 7 h of 1.7% from the ointment, 0.7% from the fatty ointment and 0.5% for the cream by combined determination through 1 intact and 1 damaged area of skin. 3. Percutaneous absorption via intact skin is slight in the case of the guinea pig also. Absorption is accelerated considerably by the removal of the stratum corneum, however, and shows a characteristic dependence on the concentration of the corticoid in the base. Whereas the corticoid from the 0.03% ointment is almost quantitatively absorbed within 7 h, absorption from the 0.5% ointment is reduced to about 30%. 4. The absolute concentrations of active ingredient in the epidermis are approximately 10(-6) mol/l and drop to approximately 10(-7) mol/l in the corium (guinea pig in vivo, man in vitro). An active ingredient flow equilibrium (inflow = outflow) is reached in the skin of the guinea pig after only 1 h.