Transdermal drug delivery and cutaneous metabolism.
Guy-RH; Hadgraft-J; Bucks-DA
Xenobiotica 1987 Aug; 17(3):325-343
The transdermal delivery of systemic therapeutic agents was reviewed. The advantages of the skin as a route for drug administration included elimination of gastrointestinal and hepatic metabolism, minimization of interpatient and intrapatient variability, maintenance of a constant drug concentration within the biophase, expansion of the duration of drug effect, reduction of the possibility of over and under dosing, simplification of the medication regiment, and easy termination of drug input at any time. The limiting factors affecting transdermal drug delivery were related to the barrier function of the skin, partitioning behavior within the stratum corneum, cutaneous metabolism, and the effect of the drug itself on the skin. Feasible transdermal drugs included those with short biological half lives which were subject to extensive first pass metabolism. The kinetic modelling of drug transfer from a transdermal system to the systemic circulation was based on equations describing drug transport between the delivery system and the stratum corneum, the partitioning and diffusion of the drug within the stratum corneum, the delivery of the drug from the stratum corneum to viable epidermal and dermal tissue, and diffusion through that tissue to the cutaneous microcirculation. The use of kinetic modelling was illustrated using drugs approved by the Food and Drug Administration for use with transdermal delivery systems such as scopolamine for the treatment of motion sickness, nitroglycerin for the treatment of heart disease, clonidine for the treatment of hypertension, and estradiol for the treatment of female menopausal symptoms. An extended model of skin absorption and transdermal delivery including biotransformation reactions associated with cutaneous metabolism was presented.
NIOSH-Publication; NIOSH-Grant; Dermatitis; Skin-absorption; Medical-treatment; Drug-therapy; Biokinetics; Pharmacodynamics
Pharmacy University of California 926 Medical Sciences Building San Francisco, CA 94143
University of California San Francisco, San Francisco, California