[Pharmacokinetics and biotransformation of diflucortolone valerate in man (author's transl)].

Two male normal subjects were each given 1 mg of 6alpha,9-difluoro-11beta-hydroxy-16alpha-methyl-21-valeryloxy-1,4-pregnadiene-3,20-dione1,2,4-3H (3H-diflucortolone valerate, Nerisona) by i.v. injection. The pharmacokinetics and biotransformation of the corticoid were examined by measurement of the total activity in the blood, plasma, urine and faeces and by thin-layer chromatographic analysis of the spectrum of the metabolites in plasma and urine. The compound is very rapidly degraded. No more intact ester was identifiable in the plasma 5 min after injection while, at the same time, 6alpha,9-difluoro-11beta,21-dihydroxy-16alpha-methyl-1,4-pregnadiene-3,20-dione (diflucortolone), the product of hydrolysis, was present in a concentration of 6-8 ng/ml plasma. The half-life of diflucortolone in the plasma was 4-5 h, that of the total 3H-steroids about 9 h. 80-40% of the 3H-steroids in the plasma were in unconjugated form. Besides diflucortolone and two unidentified metabolites chromatographic comparison demonstrated the presence of 6alpha,9-difluoro-21-hydroxy-16alpha-methyl-1,4-pregnadiene-3,11,20-trione (11-keto-diflucortolone) as a further metabolite in the plasma. The elimination was rapid and complete: by 24 h after injection approximately 56% of the dose had been eliminated with the urine and by 7 days after administration 98 and 93% of the dose had been recovered in urine and faeces. The ratio of elimination urine to faeces averaged 3:1. Within 48 h after the injection about 30% of the dose was eliminated in the form of unconjugated 3H-steroids, about 20% as 3H-steroid-glucuronides and about 10% as 3H-steroid-sulphates. Diflucortolone was demonstrable both in the unconjugated form and as glucuronide and 11-keto-diflucortolone as glucuronide and as sulphate. A total of 7 metabolites were characterized in the urine by means of chromatography.