Reverse iontophoresis: monitoring prostaglandin E2 associated with cutaneous inflammation in vivo.
In response to topical application of irritants, increased concentrations of prostaglandin E2 (PGE2) are found in human skin exudate and in cultured dermal fibroblasts. In this study, PGE2 generated in response to transdermal delivery of irritant drug compounds was monitored in hairless guinea pig (HGP) 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 PGE2 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 microA/cm2, visual scores of erythema and edema yielded a correlation with measured skin efflux of PGE2 (r = 0.86). Delivery of chlorpromazine resulted in greater efflux of PGE2 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 PGE2 efflux, indicating that the quantity of PGE2 effluxed reflects the intensity of skin irritation. In contrast, vasoconstriction or vasodilation produced by the local delivery of vasoactive agents did not correlate with PGE2 skin efflux, indicating that this measurement is specific for an inflammatory response. In summary, PGE2 generated in response to transdermally applied drug irritants can be monitored non-invasively in vivo by reverse iontophoresis.
Mize
N K
NK
Alza Corporation, Palo Alto, CA 94303, USA. nancy.mize@alza.com
Buttery
M
M
Daddona
P
P
Morales
C
C
Cormier
M
M
D000563:Amebicides / Q000009:adverse effects; D000779:Anesthetics, Local / Q000009:adverse effects; D000818:Animals; D000932:Antiemetics / Q000009:adverse effects; D001127:Arginine Vasopressin / Q000008:administration & dosage; D001692:Biological Transport / Q000187:drug effects; D001783:Blood Flow Velocity / Q000502:physiology; D002738:Chloroquine / Q000009:adverse effects; D002746:Chlorpromazine / Q000494:pharmacology; D003872:Dermatitis / Q000378:metabolism; D004890:Erythema / Q000139:chemically induced; D006168:Guinea Pigs; D007478:Iontophoresis / Q000379:methods*; D007509:Irritants / Q000494:pharmacology; D011395:Promazine / Q000009:adverse effects; D011458:Prostaglandins E / Q000378:metabolism*; D012883:Skin Ulcer / Q000139:chemically induced; D012965:Sodium Chloride / Q000494:pharmacology; D013748:Tetracaine / Q000009:adverse effects; D014662:Vasoconstrictor Agents / Q000008:administration & dosage
D000563:Amebicides; D000779:Anesthetics, Local; D000932:Antiemetics; D007509:Irritants; D011458:Prostaglandins E; D014662:Vasoconstrictor Agents; D013748:Tetracaine; D001127:Arginine Vasopressin; D012965:Sodium Chloride; D002738:Chloroquine; D011395:Promazine; D002746:Chlorpromazine