Egger N G, Motamedi M, Pow-Sang M, Orihuela E, Anderson K E
Department of Preventive Medicine and Community Health (Division of Human Nutrition, University of Texas Medical Branch, Galveston 77555-1109, USA.
Pharmacology. 1996 Jun;52(6):362-70. doi: 10.1159/000139403.
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.
给予δ-氨基乙酰丙酸后，原卟啉会在组织中蓄积，并可作为光动力疗法的光敏剂。为了确定在给予这种卟啉前体后卟啉在大型动物模型中的分布情况，给麻醉的犬静脉注射δ-氨基乙酰丙酸（100mg/kg体重），并在6 - 10小时内测量组织（肝脏、胰腺、前列腺、膀胱、肌肉和皮肤）、血浆和尿液中的卟啉浓度。卟啉在1小时内血浆中显著增加（高达50倍），在8小时时仍显著升高，且主要由粪卟啉III和原卟啉组成。组织卟啉浓度升高较慢，在给予δ-氨基乙酰丙酸后7 - 10小时，肝脏、胰腺和前列腺中的卟啉浓度最高，且主要为原卟啉。肝脏中的最大卟啉浓度分别比胰腺和前列腺高3倍和4倍。尿中δ-氨基乙酰丙酸排泄增加，给药后2 - 4小时最大；尿中卟胆原和卟啉增加较为缓慢，至少持续到8小时仍保持升高。粪卟啉III始终是尿液中的主要卟啉，但在给予δ-氨基乙酰丙酸后，七羧基、六羧基和五羧基卟啉成比例增加。这些结果表明，给予δ-氨基乙酰丙酸后，卟啉会在血浆、组织和尿液中蓄积，并可能在光动力疗法期间促成肿瘤坏死。
