5-aminolevulinic acid photosensitization of dysplastic Barrett's esophagus: A pharmacokinetic study
5-aminolevulinic acid photosensitization of dysplastic Barrett's esophagus: A pharmacokinetic study
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DOI：
10.1111/j.1751-1097.1999.tb08266.x
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发表时间：
1999-10-01
影响因子：
3.3
通讯作者：
Reed, M
中科院分区：
文献类型：
--
作者：
Ackroyd, R;Brown, N;Reed, M
使用5-氨基乙酰丙酸（ALA）诱导的原卟啉TX（PpIX）的光动力疗法（PDT）可能在治疗异型增生的Barrett食管中起作用。在ALA诱导的PDT可以用于临床之前，必须建立最佳治疗参数。在这项35例患者的研究中，讨论了口服ALA给药的药物剂量、药物和光递送之间的时间间隔以及副作用的问题。组织样本的荧光光谱分析表明，口服ALA可诱导食管组织中的卟啉积聚，在46小时达到最高水平，高效液相色谱法证实了这种卟啉的身份为PpIM，荧光显微镜分析表明它优先积聚在食管中粘膜，而不是在底层基质中，ALA给药的副作用包括不适、头痛、光敏性、脱发、短暂性肝功能紊乱、恶心和呕吐。与50 mg/kg ALA相比，30 mg/kg ALA的副作用更少，肝毒性更小。总之，口服ALA给药诱导食管粘膜中优先的PpIX积累，在4 h时观察到峰值PpIX荧光，并且在30 mg/kg剂量下全身毒性最小。
Photodynamic therapy (PDT) using 5-aminolevulinic acid (ALA)-induced protoporphyrin TX (PpIX) may have a role in the treatment of dysplastic Barrett's esophagus, Before ALA-induced PDT can be used clinically, optimum treatment parameters must be established. Ln this study of 35 patients, the issues of drug dosage, time interval between drug and light delivery and side effects of oral ALA administration are addressed. Spectrofluorometric analysis of tissue samples demonstrates that oral ALA administration induces porphyrin accumulation in esophageal tissues, with maximum levels at 46 h, High-performance liquid chromatography confirms the identity of this porphyrin as PpIM, and fluorescence microscopy analysis demonstrates that it preferentially accumulates in the esophageal mucosa, rather than in the underlying stroma, Side effects of ALA administration included malaise, headache, photosensitivity, alopecia, transient derangement of liver function, nausea and vomiting. Fewer side effects and less hepatic toxicity was seen with 30 mg/kg than 50 mg/kg ALA, Ln conclusion, oral ALA administration induces preferential PpIX accumulation in the esophageal mucosa, with peak PpIX fluorescence noted at 4 h and minimal systemic toxicity at a dose of 30 mg/kg.