Tissue distribution and kinetics of endogenous porphyrins synthesized after topical application of ALA in different vehicles.
The use of 5-aminolaevulinic acid (ALA) is gaining increasing attention for photosensitization in photodynamic therapy of superficially localized tumours. The aim of this work was to determine the kinetics of porphyrin generation in tissues after topical application of ALA delivered in different vehicles on the skin overlying the tumour and normal skin of mice. Maximal accumulation was found in tumour 3 h after ALA application in both cream and lotion preparations. Normal and overlying tumour skin tissues showed different kinetic patterns, reflecting histological changes when the latter is invaded by tumour cells. Liver, kidney, spleen and blood porphyrins also raised from basal levels, showing that ALA and/or ALA-induced porphyrins reach all tissues after topical application. During the first 24 h of ALA topical application, precursors and porphyrins are excreted by both urine and faeces. ALA lotion applied on the skin overlying the tumour induced higher accumulation of tumoural porphyrins than cream, and lotion applied on normal skin appeared to be the most efficient upon inducing total body porphyrins. This work has demonstrated the great influence of the formulation of ALA vehicle on penetration through the skin. Knowledge of the kinetics of porphyrin generation after different conditions of ALA application is needed for the optimization of diagnosis and phototherapy in human tumours.
Casas
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A
Centro de Investigaciones sobre Porfirinas y Porfirias, FCEyN (University of Buenos Aires) and CONICET; Ciudad Universitaria, Capital Federal, Argentina.
Fukuda
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H
Batlle
A M
AM
D000230:Adenocarcinoma / Q000188:drug therapy / Q000378:metabolism; D000287:Administration, Topical; D000622:Aminolevulinic Acid / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D000818:Animals; D007700:Kinetics; D008297:Male; D008325:Mammary Neoplasms, Experimental / Q000188:drug therapy / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D009368:Neoplasm Transplantation; D014677:Pharmaceutical Vehicles / Q000008:administration & dosage / Q000494:pharmacology*; D017319:Photosensitizing Agents / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D011166:Porphyrins / Q000096:biosynthesis* / Q000097:blood; D014018:Tissue Distribution
D014677:Pharmaceutical Vehicles; D017319:Photosensitizing Agents; D011166:Porphyrins; D000622:Aminolevulinic Acid