Abstract
The aim of the current investigation was to evaluate the percutaneous absorption of the synthetic cannabinoid WIN 55,212-2 in vitro and in vivo. The in vitro permeation studies of WIN 55,212-2 in human skin, hairless guinea pig skin, a polymer membrane with adhesive, and a skin/polymer membrane composite were conducted in flowthrough diffusion cells. The pharmacokinetic parameters for WIN 55,212-2 were determined after intravenous administration and topical application of Hill Top Chambers and transdermal therapeutic systems (TTS) in guinea pigs. The in vitro permeation studies indicated that the flux of WIN 55,212-2 through hairless guinea pig skin was 1.2 times more than that through human skin. The flux of WIN 55,212-2 through human and guinea pig skin was not significantly higher than that through the corresponding skin/polymer membrane composites. The mean guinea pig steady-state plasma concentrations after topical 6.3 cm2 chamber and 14.5 cm2 TTS patch applications were 5.0 ng/ml and 8.6 ng/ml, respectively. The topical drug treatments provided significant steady-state plasma drug levels for 48 h. The observed in vivo results from the Hill Top Chambers and TTS patches in the guinea pigs were in good agreement with the predicted plasma concentrations from the in vitro data.
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