Effect of transdermal iontophoresis codelivery of hydrocortisone on metoclopramide pharmacokinetics and skin-induced reactions in human subjects

The effects of transdermal iontophoresis (IP) codelivery of hydrocortisone (HC) on metoclopramide hydrochloride (MCP) pharmacokinetics and on skin-ind uced reactions were evaluated in a randomized, crossover clinical study. MC P, an antiemetic, low molecular weight, cationic drug intended for systemic delivery, was delivered from the anode of IP systems at a constant current of 100 mu A/cm(2). HC, a neutral endogenous antiinflammatory agent, was co delivered from the same electrode, primarily by electroosmotic processes. E ach subject (n = 7) wore two identical IP systems (MCP alone or MCP plus HC ), each supplying 500 mu A, one on each upper arm for 4 h. One week later, each subject repeated the procedure with the alternate type of MCP system. HC did not change the pharmacokinetics of MCP: There were no statistically significant differences in MCP plasma concentrations, half-life, area under the curve (AUC), or rate of absorption between the two treatment groups. H owever, HC significantly decreased erythema and edema scores produced by th e IP of MCP. In both groups, a steady-state MCP flux of about 100 mu g/(cm( 2) x h) was achieved after only 1 h of transport, and input rate dropped dr amatically immediately after removal of the system. In vitro, HC flux throu gh human epidermis from an MCP plus HC formulation was 2.8 +/- 1.1 mu g/(cm (2) x h) after 4 h transport at 100 mu A/cm(2), suggesting negligible syste mic exposure to hydrocortisone. These data indicate that MCP input rate and its clearance from the skin are unaltered by HC and that the codelivery of HC by IP is an effective strategy for inhibition of local reactions result ing from the transdermal delivery of drugs.