Side effects and photosensitization of human tissues after aminolevulinic acid.

Abstract

Aminolevulinic acid (ALA) is being used as a "prodrug" for photodynamic therapy. The side effects of ALA have been only anecdotally reported and these effects as well as pharmacokinetics of the photosensitizing end product of ALA, protoporphyrin IX (PpIX), in patients undergoing operation are unknown. This study systematically determines the side effects of ALA and pharmacokinetics of PpIX in patients undergoing abdominal surgery. Patients were given 30 or 60 mg/kg ALA preoperatively, kept in subdued light for 48 hr, and monitored clinically and with laboratory tests for 5 to 7 days and for at least 2 months thereafter. Periodic plasma samples and tissue biopsies were analyzed for PpIX concentrations using a photodiode array system. No patient developed symptoms of porphyria other than nausea and vomiting, which occurred in 20%. Nearly one-quarter of patients developed transient abnormal liver functions. No patient developed cutaneous phototoxicity, abnormal neurologic function, or unexpected postoperative laboratory tests. The times of peak plasma, skin, skeletal muscle, omental, mucosal, muscularis mucosal, and tumor concentrations of PpIX varied among patients. In general, PpIX concentrations were significantly greater with the higher dose of ALA. Tumor PpIX concentrations were significantly greater than in other tissues except liver. In conclusion, ALA, up to 60 mg/kg, is associated with minimal side effects in patients undergoing operation. Actual tissue concentrations of PpIX suggest that endogenous photosensitization using systemically administered ALA is a mode of PDT feasible for treatment of adenocarcinomas of the gastrointestinal tract in humans.

• Authors: J Webber, D Kessel, D Fromm
• Journal: The Journal of surgical research (J Surg Res) Vol. 68 Issue 1 Pg. 31-7 (Feb 15 1997) ISSN: 0022-4804 [Print] United States
• PMID: 9126192 (Publication Type: Clinical Trial, Controlled Clinical Trial, Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Photosensitizing Agents
• Protoporphyrins
• Aminolevulinic Acid
• protoporphyrin IX

Topics

• Adenocarcinoma (drug therapy, metabolism)
• Administration, Oral
• Aminolevulinic Acid (administration & dosage, adverse effects, therapeutic use)
• Female
• Gastrointestinal Neoplasms (drug therapy, metabolism)
• Humans
• Liver (drug effects)
• Liver Function Tests
• Male
• Nausea (chemically induced)
• Photochemotherapy
• Photosensitizing Agents (pharmacokinetics)
• Protoporphyrins (pharmacokinetics)
• Tissue Distribution
• Vomiting (chemically induced)