Abstract

Transdermal drug delivery seems a promising way of achieving complete, predictable absorption, but the epidermis is a barrier for most drugs. A new technique for transdermal drug delivery, in which a small patch of epidermis was removed, was tested in seven healthy volunteers by means of the antidiuretic peptide 1-deamino-8-D-arginine vasopressin (DDAVP). The epithelium of a small area of forearm skin (diameter 5 mm) was removed painlessly, and in a standard way, by a simple device operating at a present vacuum. DDAVP was given by way of improvised occlusive reservoirs. Plasma DDAVP concentration/time curves conformed closely with zero-order kinetics, which suggests that the bioavailability approached 100%, corresponding to that for direct intravenous infusion. Four volunteers were given DDAVP daily for 4 days by way of the de-epithelialised site; there were no signs that re-epithelialisation hindered permeation. All plasma DDAVP values substantially exceeded the lowest effective therapeutic concentration for patients with diabetes insipidus. The vacuum removal of the epithelium caused pronounced hyperaemia in the de-epithelialised dermis (assessed by laser doppler flow measurement); the hyperaemia persisted, unaffected by DDAVP, and may have contributed to the efficient permeation. The skin spot appeared normal at 6 weeks.