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Comparison of the Pharmacokinetics and Phototoxicity of Protoporphyrin IX Metabolized from 5‐Aminolevulinic Acid and Two Derivatives in Human Skin In Vivo ¶
Author(s) -
Gerscher Sandra,
Connelly James P.,
Griffiths John,
Brown Stanley B.,
MacRobert Alexander J.,
Wong Gavin,
Rhodes Lesley E.
Publication year - 2000
Publication title -
photochemistry and photobiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.818
H-Index - 131
eISSN - 1751-1097
pISSN - 0031-8655
DOI - 10.1562/0031-8655(2000)0720569cotpap2.0.co2
Subject(s) - phototoxicity , protoporphyrin ix , in vivo , pharmacokinetics , protoporphyrin , pharmacology , human skin , chemistry , biochemistry , in vitro , medicine , biology , photodynamic therapy , organic chemistry , porphyrin , genetics
Our novel approach was to compare the pharmacokinetics of 5‐aminolevulinic acid (ALA), ALA‐ n ‐butyl and ALA‐ n ‐hexylester induced protoporphyrin IX (PpIX), together with the phototoxicity after photodynamic therapy (PDT) in human skin in vivo, using iontophoresis as a dose‐control system. A series of four increasing doses of each compound was iontophoresed into healthy skin of 10 volunteers. The kinetics of PpIX metabolism (n = 4) and the response to PDT (n = 6) performed 5 h after iontophoresis, were assessed by surface PpIX fluorescence and post‐irradiation erythema. Whilst ALA‐induced PpIX peaked at 7.5 h, highest PpIX fluorescence induced by ALA‐ n ‐hexylester was observed at 3–6 h and no clear peak was seen with ALA‐ n ‐butylester. With ALA‐ n ‐hexylester, more PpIX was formed after 3 ( P < 0.05) and 4.5 h, than with ALA or ALA‐ n ‐butylester. All compounds showed a linear correlation between logarithm of dose and PpIX fluorescence/phototoxicity at 5 h, with R ‐values ranging from 0.87 to 1. In addition, the ALA‐ n ‐hexylester showed the tendency to cause greater erythema than ALA and ALA‐ n ‐butylester. Fluorescence microscopy (n = 2) showed similar PpIX distributions and penetration depths for the three drugs, although both ALA esters led to a more homogeneous PpIX localization. Hence, ALA‐ n ‐hexylester appears to have slightly more favorable characteristics for PDT than ALA or ALA‐ n ‐butylester.