ACCUMULATION OF PORPHYRINS IN PLASMA AND TISSUES OF DOGS AFTER DELTA-AMINOLEVULINIC-ACID ADMINISTRATION - IMPLICATIONS FOR PHOTODYNAMIC THERAPY

Protoporphyrin accumulates in tissues after administration of delta-am inolevulinic acid, and can be used as a photosensitizer for photodynam ic therapy. To determine the distribution of porphyrins in a large ani mal model after administration of this porphyrin precursor, delta-amin olevulinic acid was administered to anesthetized dogs (100 mg/kg body weight intravenously) and porphyrin concentrations were measured in ti ssues (liver, pancreas, prostate, bladder, muscle and skin), plasma an d urine for 6-10 h. Porphyrins increased markedly (up to 50-fold) in p lasma within 1 h, were still markedly increased at 8 h, and consisted mostly of coproporphyrin III and protoporphyrin. Tissue porphyrin conc entrations increased more slowly. were highest in liver, pancreas and prostate 7-10 h after delta-aminolevulinic acid administration, and we re predominantly protoporphyrin. Maximum porphyrin concentrations in l iver were 3- and 4-fold higher than in pancreas and prostate, respecti vely. Urinary delta-aminolevulinic acid excretion increased and was gr eatest 2-4 h after dosing, urinary porphobilinogen and porphyrins incr eased more gradually and remained increased up to at least 8 h. Coprop orphyrin III was the predominant porphyrin in urine at all times. but hepta-, hexa- and pentacarboxyl porphyrins increased proportionally af ter administration of delta-aminolevulinic acid. These results indicat e that porphyrins accumulate in plasma as well as tissues and urine af ter administration of delta-aminolevulinic acid, and may contribute to tumor necrosis during photodynamic therapy.