Original Article

Journal of Investigative Dermatology (1997) 108, 87–91; doi:10.1111/1523-1747.ep12285644

Iontophoretic Delivery of ALA Provides a Quantitative Model for ALA Pharmacokinetics and PpIX Phototoxicity in Human Skin

Lesley E Rhodes, Maria M Tsoukas, R Rox Anderson and Nikiforos Kollias

Wellman Laboratories of Photomedicine, Massachusetts General Hospital, Harvard University, Boston, Massachusetts, U.S.A.

Received 13 May 1996; Revised 15 August 1996; Accepted 29 August 1996.

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Abstract

Photodynamic therapy (PDT) with topical 5-aminolevulinic acid (ALA) is increasingly employed for skin cancer, yet ALA dosing is crude. Using iontophoresis, we developed a rapid and quantifiable system for topical ALA delivery, with measurement of subsequent PpIX fluorescence and phototoxicity. ALA was iontophoresed from a 2% solution into upper inner arm skin of 13 healthy volunteers. Six doses of ALA were delivered with a series of charges varying from 3-120 milliCoulombs (mC); four additional doses were given with a charge of 60 mC. Five hours post-iontophoresis, sites were irradiated with broad-band yellow-red light, the series of six ALA doses receiving 100 J/cm2, while the four identical doses received 6.25, 12.5, 25 and 50 J/cm2, respectively. Resultant erythema was measured by reflectance spectroscopy. The time course of PpIX fluorescence was ALA-dose-dependent. With charge less than or equal to 24 mC, PpIX fluorescence peaked at 3 h and returned to zero at 9-10 h, whereas charges > 24 mC had a sustained peak at 5-10 h, falling to zero by 24 h. Pre-irradiation, PpIX fluorescence correlated with ALA dose (r = 1.0). PpIX fluorescence fell immediately post-irradiation (p < 0.0001); recovery levels at 3 h correlated with ALA dose (p < 0.0001). Delayed erythema correlated with ALA dose and irradiation dose (p < 0.0001, p < 0.01, respectively). Both PpIX fluorescence intensity pre-irradiation and fall in PpIX fluorescence post-irradiation correlated with erythema (r = 0.98). Hence, PpIX synthesis is ALA-dose-dependent and phototoxicity can be predicted from ALA dose, irradiation dose and photobleaching of PpIX. This reproducible system allows accurate dosimetry in topical PDT and facilitates study of ALA metabolism.

Keywords:

photobleaching, photodynamic therapy, iontophoresis

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