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.
Günther
C
C
Institute of Pharmacokinetics, Schering AG, Berlin, Germany.
Kecskes
A
A
Staks
T
T
Täuber
U
U
D000269:Adhesives; D000287:Administration, Topical; D000368:Aged; D000893:Anti-Inflammatory Agents / Q000009:adverse effects / Q000493:pharmacokinetics*; D003872:Dermatitis / Q000188:drug therapy* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004655:Emulsions; D004890:Erythema / Q000188:drug therapy / Q000378:metabolism; D006801:Humans; D008297:Male; D008775:Methylprednisolone / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D008875:Middle Aged; D012016:Reference Values; D012869:Skin Absorption; D013471:Sunburn / Q000188:drug therapy* / Q000378:metabolism; D013499:Surface Properties; D014466:Ultraviolet Rays
D000269:Adhesives; D000893:Anti-Inflammatory Agents; D004655:Emulsions; C078007:methylprednisolone aceponate; D008775:Methylprednisolone