MICRODIALYSIS IN CUTANEOUS PHARMACOLOGY - KINETIC-ANALYSIS OF TRANSDERMALLY DELIVERED NICOTINE

Direct measurements of cutaneous drug levels and kinetics have long been hampered by lack of appropriate methods. Recently, studies have indicated that microdialysis, a method of continuous in vivo sampling of extracellular fluid, may also be performed in human skin. The present study was designed to evaluate this technique for kinetic analyses of cutaneous drug levels. Using a transdermal nicotine delivery system with 35 mg of nicotine as a model, nicotine levels were determined in the dialysate of human skin by means of high performance liquid chromatography. In vitro studies demonstrated that nicotine levels in the dialysate strictly correlated with nicotine concentrations in the dialyzed medium. In nine healthy male volunteers receiving nicotine by transdermal delivery, nicotine was detectable within 90-180 min, and peak levels of approximately 1000 ng/ml were detected within 240-360 min of patch application. Correlation analyses of the individual data from our subjects revealed that nicotine kinetics were independent of skin barrier function, as assessed by transepidermal water loss, but indicated that the detectable maximum nicotine levels may depend on the location of the probe. In summary, the present study demonstrates that microdialysis may be a novel, powerful tool to study cutaneous pharmacology in vivo.