1 May 1995 Tissue-dependent biosynthesis and pharmacokinetics of Protopophyrin IX following intravenous injection of δ-aminolevulinic acid
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Abstract
Two significant questions arise when a drug for photodynamic therapy is introduced to the preclinical arena: (1) pharmacokinetics for the uptake and elimination and (2) relative retention by various tissues. Theses were addressed by following the pharmacokinetics in 21 rabbits with 130 tumors at different drug doses and at time intervals ranging from minutes to 24 hours. Kinetics were studied spectrofluorometrically by following extracting Protoporphyrin IX (PPIX), a metabolite of delta- aminolevulinic acid (ALA). Samples were compared to a standard, and are thus quantitative. The rise time in plasma was rapid, and reached maximum one hour post injection with drug doses of 50, 100, and 200 mg/kg. The single exponential fall time displayed a half life of fifty minutes, resulting in a complete elimination of PPIX in 24 hours. Uptake and retention in multiple tissues were measured 3 hours post injection of 100 mg/g ALA in 3 animals, with skin, tumor, and plasma measured in all 21 animals. Organs with high vascularity displayed higher values of PPIX. Results of this study indicate that ALA utilized as a systemically administered sensitizer maybe of significant value in PDT of selected tumor types.
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Avigdor M. Ronn, Lennart A. Lofgren, "Tissue-dependent biosynthesis and pharmacokinetics of Protopophyrin IX following intravenous injection of δ-aminolevulinic acid", Proc. SPIE 2392, Optical Methods for Tumor Treatment and Detection: Mechanisms and Techniques in Photodynamic Therapy IV, (1 May 1995); doi: 10.1117/12.208177; https://doi.org/10.1117/12.208177
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