Percutaneous Absorption of Methylprednisolone Aceponate following Topical Application of Advantan® Lotion on Intact, Inflamed and Stripped Skin of Male Volunteers

Six healthy, elderly volunteers received three topical treatments with Advantan® lotion containing 0.1% of methylprednisolone aceponate (MPA, CAS 86401-95-8) on intact, inflamed and stripped skin in a consecutive fashion at weekly intervals. The lotion (O/W emulsion) containing 14C-MPA (specific radioactivity 1.8 MBq/mg MPA) was applied in an area dose of 5 mg lotion/cm2 on a marked area of 100 cm2 on the back for 24 h. Inflammation was caused by UV-B irradiation at 3 MED 6 h prior to the treatment with the test preparation. Removal of stratum corneum was performed by 20-fold adhesive tape stripping. The concentration of radioactivity was measured in the plasma and in the urine up to 7 days following each treatment. The concentration of radioactivity in the plasma did not exceed the limit of detection of 1.5 ng MPA Eq/ml at any time point. The percutaneous absorption was assessed from the cumulated excretion of radiolabelled substances in the urine corrected for biliary excretion. Less than 0.5% of the dose was percutaneously absorbed through intact skin and through inflamed skin. After removal of the penetration barrier (‘stripping’) the percutaneous absorption increased to 15.4±7.7% of the applied dose.