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-aminolevulinic acid, and can be used as a photosensitizer for photodynamic therapy. To determine the distribution of porphyrins in a large animal model after administration of this porphyrin precursor, delta-aminolevulinic acid was administered to anesthetized dogs (100 mg/kg body weight intravenously) and porphyrin concentrations were measured in tissues (liver, pancreas, prostate, bladder, muscle and skin), plasma and urine for 6-10 h. Porphyrins increased markedly (up to 50-fold) in plasma within 1 h, were still markedly increased at 8 h, and consisted mostly of coproporphyrin III and protoporphyrin. Tissue porphyrin concentrations increased more slowly, were highest in liver, pancreas and prostate 7-10 h after delta-aminolevulinic acid administration, and were predominantly protoporphyrin. Maximum porphyrin concentrations in liver were 3- and 4-fold higher than in pancreas and prostate, respectively. Urinary delta-aminolevulinic acid excretion increased and was greatest 2-4 h after dosing; urinary porphobilinogen and porphyrins increased more gradually and remained increased up to at least 8 h. Coproporphyrin III was the predominant porphyrin in urine at all times, but hepta-, hexa- and pentacarboxyl porphyrins increased proportionally after administration of delta-aminolevulinic acid. These results indicate that porphyrins accumulate in plasma as well as tissues and urine after administration of delta-aminolevulinic acid, and may contribute to tumor necrosis during photodynamic therapy.
Egger
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NG
Department of Preventive Medicine and Community Health (Division of Human Nutrition, University of Texas Medical Branch, Galveston 77555-1109, USA.
Motamedi
M
M
Pow-Sang
M
M
Orihuela
E
E
Anderson
K E
KE
D000622:Aminolevulinic Acid / Q000008:administration & dosage* / Q000378:metabolism / Q000627:therapeutic use; D000818:Animals; D003306:Coproporphyrins / Q000097:blood / Q000652:urine; D004285:Dogs; D008099:Liver / Q000378:metabolism; D008297:Male; D009369:Neoplasms / Q000188:drug therapy; D010179:Pancreas / Q000378:metabolism; D010778:Photochemotherapy; D011166:Porphyrins / Q000097:blood* / Q000652:urine; D011467:Prostate / Q000378:metabolism
D003306:Coproporphyrins; D011166:Porphyrins; C026971:coproporphyrin III; D000622:Aminolevulinic Acid