REVERSE IONTOPHORESIS - MONITORING PROSTAGLANDIN E-2 ASSOCIATED WITH CUTANEOUS INFLAMMATION IN-VIVO

In response to topical application of irritants, increased concentrati ons of prostaglandin E-2 (PGE(2)) are found in human skin exudate and in cultured dermal fibroblasts. In this study, PGE(2) generated in res ponse to transdermal delivery of irritant drug compounds was monitored in hairless guinea pig (HGP) by a non-invasive method, reverse iontop horesis. Reverse iontophoresis is the movement of molecules from the s kin under the influence of an applied electric field. Irritant drug co mpounds were applied with iontophoresis (electrotransport), and revers e iontophoresis of PGE(2) from skin was monitored by radioimmunoassay (RIA) after extraction from the delivery system. Chlorpromazine was us ed as a model drug irritant. When chlorpromazine and saline were appli ed over a range of current densities from 0 to 200 mu A/cm(2), visual scores of erythema and edema yielded a correlation with measured skin efflux of PGE(2) (r = 0.86). Delivery of chlorpromazine resulted in gr eater efflux of PGE(2) than delivery of non-irritant saline controls u nder the same delivery conditions, Five drug compounds, chloroquine, p romazine, chlorpromazine. tetracaine, metoclopramide, and saline were applied to hairless guinea pig skin. The 6 agents were similarly rank ordered by visual erythema/edema scores and by PGE(2) efflux, indicati ng that the quantity of PGE(2) effluxed reflects the intensity of skin irritation. In contrast, vasoconstriction or vasodilation produced by the local delivery of vasoactive agents did not correlate with PGE(2) skin efflux, indicating that this measurement is specific for an infl ammatory response. In summary, PGE(2) generated in response to transde rmally applied drug irritants can be monitored non-invasively in vivo by reverse iontophoresis.