5-Aminolevulinic acid photosensitization of dysplastic Barrett's esophagus: a pharmacokinetic study.
Photodynamic therapy (PDT) using 5-aminolevulinic acid (ALA)-induced protoporphyrin IX (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. In 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 4-6 h. High-performance liquid chromatography confirms the identity of this porphyrin as PpIX, 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. In 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.
Ackroyd
R
R
Department of Surgical and Anaesthetic Sciences, University of Sheffield, UK.
Brown
N
N
Vernon
D
D
Roberts
D
D
Stephenson
T
T
Marcus
S
S
Stoddard
C
C
Reed
M
M
D000622:Aminolevulinic Acid / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001471:Barrett Esophagus / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D011524:Protoporphyrins / Q000378:metabolism
D017319:Photosensitizing Agents; D011524:Protoporphyrins; D000622:Aminolevulinic Acid; C028025:protoporphyrin IX