FEASIBILITY OF MEASURING LIPOPHILIC OR PROTEIN-BOUND DRUGS IN THE DERMIS BY IN-VIVO MICRODIALYSIS AFTER TOPICAL OR SYSTEMIC DRUG ADMINISTRATION

Our aim was to assess the microdialysis technique for determining in v ivo drug levels of a lipophilic and a protein-bound model drug in the dermis. Forearm skin of healthy volunteers received topical 2% fusidic acid or 0.1% betamethasone-17-valerate formulations twice daily as oc cluded treatment on irritative dermatitis. Microdialysis sampling in t he dermis after 48 h was without measurable drug. Hairless rats receiv ed maximized treatment with occluded applications of 10% fusidic acid or 4% betamethasone-17-valerate in ethanol for 72 h followed by microd ialysis. Mean levels of betamethasone-17-valerate were 11 - 45 ng/ml; fusidic acid was not measurable. Systemic administration in clinical d oses to rats was without measurable drug levels; increasing doses to 3 12 mg/kg of fusidic acid and 158 mg/kg of betamethasone-17-valerate yi elded betamethasone-17-valerate levels of 25 - 44 ng/ml and fusidic ac id levels of 10 - 90 ng/ml. This study demonstrates the challenges ari sing when using microdialysis for measuring ill vivo-drug levels. For the drugs chosen it was necessary to administer very high systemic dos es or apply a high topical drug concentration to obtain measurable dru g levels in the dialysates. Drug levels were in the nanomolar range an d demonstrated reproducible and dynamic monitoring of in vivo drug lev els in the skin. Using microdialysis for sampling highly protein-bound or lipophilic drugs in the skin requires very sensitive analytical me thods, and the sensitivity of the analysis is likely to be the limitin g factor.