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Reverse iontophoresis: monitoring prostaglandin E 2 associated with cutaneous inflammation in vivo
Author(s) -
Mize Nancy K.,
Buttery Margaret,
Daddona Peter,
Morales Claudia,
Cormier Michel
Publication year - 1997
Publication title -
experimental dermatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.108
H-Index - 96
eISSN - 1600-0625
pISSN - 0906-6705
DOI - 10.1111/j.1600-0625.1997.tb00176.x
Subject(s) - iontophoresis , pharmacology , transdermal , chemistry , erythema , prostaglandin e , saline , edema , medicine , anesthesia , dermatology , biochemistry , radiology
In response to topical application of irritants, increased concentrations of prostaglandin E 2 (PGE 2 ) are found in human skin exudate and in cultured dermal fibroblasts. In this study, PGE 2 generated in response to transdermal delivery of irritant drug compounds was monitored in hairless guinea pig (HOP) by a non‐invasive method, reverse iontophoresis. Reverse iontophoresis is the movement of molecules from the skin under the influence of an applied electric field. Irritant drug compounds were applied with iontophoresis (electrotransport), and reverse iontophoresis of PGE 2 from skin was monitored by radioimmunoassay (RIA) after extraction from the delivery system. Chlorpromazine was used as a model drug irritant. When chlorpromazine and saline were applied over a range of current densities from 0 to 200 μA/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 greater efflux of PGE 2 than delivery of non‐irritant saline controls under the same delivery conditions. Five drug compounds, chloroquine, promazine, 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, indicating 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 inflammatory response. In summary, PGE 2 generated in response to transdermally applied drug irritants can be monitored non‐invasively in vivo by reverse iontophoresis.