In vivo pharmacokinetics of protoporphyrin IX accumulation following intracutaneous injection of 5-aminolevulinic acid

Photodynamic therapy with 5-aminolevulinic acid (ALA) derived protoporphyri n IX (PpIX) as photosensitizer is a promising treatment for basal cell carc inomas. Until now ALA has been administered topically as an oil-in-water cr eam in most investigations. The disadvantage of this administration route i s insufficient penetration in deeper, nodular tumours. Therefore we investi gated intracutaneous injection of ALA as an alternative administration rout e. ALA was administered in 6-fold in the normal skin of three 6-week-old fe male Dutch pigs by intracutaneous injection of an aqueous solution of ALA ( pH 5.0) in volumes of 0.1-0.5 ml and concentrations of 0.5-2% and by topica l administration of a 20% ALA cream. During 8 h fluorescence of ALA derived PpIX was measured under 405 nm excitation. For the injection the measured fluorescence was shown to be dose dependent. All injected doses of 3 mg ALA or more lead to a faster initial increase rate of PpIX synthesis and signi ficantly greater fluorescence than that measured after topical administrati on of ALA. Irradiation (60 Jcm(-2) for 10 min) of the spots was performed a t 3.5 h after ALA administration. After 48 and 96 h visual damage scores we re evaluated and biopsies were taken for histopathological examination. Aft er injection of 2 mg ALA or more the PDT damage after illumination was show n to be significantly greater than after topical application of 20% ALA. An injected dose of 10 mg ALA (0.5 ml of a 2% solution) resulted in significa ntly more tissue damage after illumination than all other injected doses. ( C) 2001 Elsevier Science BY All rights reserved.