M. Cormier et al., Effect of transdermal iontophoresis codelivery of hydrocortisone on metoclopramide pharmacokinetics and skin-induced reactions in human subjects, J PHARM SCI, 88(10), 1999, pp. 1030-1035
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.