PERCUTANEOUS-ABSORPTION OF METHYLPREDNISOLONE ACEPONATE FOLLOWING TOPICAL APPLICATION OF ADVANTAN(R) LOTION ON INTACT, INFLAMED AND STRIPPED SKIN OF MALE-VOLUNTEERS

Six healthy, elderly volunteers received three topical treatments with Advantan(R) lotion containing 0.1% of methylprednisolone aceponate (M PA, CAS 86401-95-8) on intact, inflamed and stripped skin in a consecu tive fashion at weekly intervals. The lotion (O/W emulsion) containing C-14-MPA (specific radioactivity 1.8 MBq/mg MPA) was applied in an ar ea dose of 5 mg lotion/cm(2) on a marked area of 100 cm(2) on the back for 24 h. Inflammation was caused by UV-B irradiation at 3 MED 6 h pr ior to the treatment with the test preparation. Removal of stratum cor neum was performed by 20-fold adhesive tape stripping. The concentrati on 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 c umulated excretion of radiolabelled substances in the urine corrected for biliary excretion. Less than 0.5% of the dose was percutaneously a bsorbed through intact skin and through inflamed skin. After removal o f the penetration barrier ('stripping') the percutaneous absorption in creased to 15.4 +/- 7.7% of the applied dose.