PHARMACOKINETICS OF 5-AMINOLEVULINIC ACID-INDUCED PROTOPORPHYRIN-IX IN SKIN AND BLOOD

The fluorescence and photosensitivity of endogenously synthesized prot oporphyrin IX (PPIX) is increasingly used for the diagnosis and treatm ent of malignant and certain non-malignant diseases. A selective accum ulation of PPIX can be induced by application of 5-aminolevulinic acid (5-ALA), which is a precursor of PPIX in the cellular biosynthetic pa thway of heme. The purpose of this study was to monitor the in vivo ac cumulation of PPIX in different locations of the skin after oral inges tion and to determine the pharmacokinetics of 5-ALA and PPIX in human blood plasma for various routes of application. At the same time we wa nted to achieve an optimal treatment scheme but also study possible si de-effects of 5-ALA administration. After oral application of 5-ALA in a concentration of 40 mg kg(-1) body weight, the fluorescence intensi ties of PPIX in the skin showed maxima between 6.5 and 9.8 h depending on the location and decreased to values lower than 5% related to the maximum after a mean time of about 40 h, The measured absolute intensi ties of PPIX fluorescence varied strongly between different patients a nd different locations on one patient, Ln the plasma of blood samples, PPIX could be detected via its fluorescence for all studied routes of application with the exception of the ointment, where PPIX levels wer e below the detection limit of 1 mu g l(-1). The highest mean concentr ation of 742 mu g l(-1) PPIX in the plasma was measured 6.7 h after or al application, For inhalation of 5-ALA, a mean maximum concentration of 12 mu g l(-1) could be detected 4.1 h after application, for intrav esical instillation, the mean maximum concentration was found to be 1 mu g l(-1) 2.9 h after application. The kinetics of 5-ALA in the plasm a peaked much earlier with a maximum concentration of 32 mg l(-1) abou t 30 min. after oral administration. The 5-ALA levels did not exceed n ormal reference values after topical application. The results of our e xperiments suggest that for a systemic application of 5-ALA side-effec ts in sensitive patients cannot be excluded. (C) 1997 Elsevier Science S.A.