TY - JOUR
T1 - Accumulation of porphyrins in plasma and tissues of dogs after δ-aminolevulinic acid administration
T2 - Implications for photodynamic therapy
AU - Eggeri, Norman G.
AU - Motamedi, Massoud
AU - Pow-Sang, Mariela
AU - Orihuela, Eduardo
AU - Anderson, Karl E.
PY - 1996/1/1
Y1 - 1996/1/1
N2 - Protoporphyrin accumulates in tissues after administration of δ-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, δ-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 δ-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 δ-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 δ-aminolevulinic acid. These results indicate that porphyrins accumulate in plasma as well as tissues and urine after administration of δ-aminolevulinic acid, and may contribute to tumor necrosis during photodynamic therapy.
AB - Protoporphyrin accumulates in tissues after administration of δ-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, δ-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 δ-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 δ-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 δ-aminolevulinic acid. These results indicate that porphyrins accumulate in plasma as well as tissues and urine after administration of δ-aminolevulinic acid, and may contribute to tumor necrosis during photodynamic therapy.
KW - Cancer
KW - Photodynamic therapy
KW - Porphyrins
KW - Protoporphyrin
KW - δ-Aminolevulinic acid
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U2 - 10.1159/000139403
DO - 10.1159/000139403
M3 - Article
C2 - 8844786
AN - SCOPUS:0029824659
SN - 0031-7012
VL - 52
SP - 362
EP - 370
JO - Pharmacology
JF - Pharmacology
IS - 6
ER -