Intravesical administration of 5-aminolevulinic acid (5-ALA) - Safety and pharmacokinetics of 5-ALA and its metabolite protoporphyrin IX

Objective: In an open study, the local and systemic side effects and pharma cokinetics of 5-amino-levulinic acid (5-ALA) and the fluorescent metabolite protoporphyrin IX (PPIX) were investigated after intravesical administrati on for the fluorescent photodetection of superficial bladder carcinoma. Patients and methods: In 20 patients with confirmed bladder carcinoma, 5-AL A was introduced into the bladder 2 h (15 patients) and 4 h (5 patients) be fore an elective endoscopic resection. The 5-ALA and PPIX levels in the pla sma were determined before and up to 10 h after application, and in the uri ne 2 h or 4 h after application. Results: The plasma level of 5-ALA rose rapidly, the maximal concentration (340 ng/ml) being reached in 0.55 h (2 h) or 0.62 h (4 h). The elimination half-life of 5-ALA amounted to 0.74 h (2 h) or 0.79 h (4 h). In five of the patients, there was a measurable plasma concentration which ranged from th e detection limit of 4.3 ng/ml to 14 ng/ml between 2 h and 5 h after applic ation, and then fell below the detection limit after 9 h. Absorption of 5-A LA by the bladder was low, i.e. less than 1% of the total amount applied. D uring a period of observation of 96 h, no 5-ALA-specific side effects appea red. Conclusion: Because of the small quantity of 5-ALA resorbed following its i ntravesical administration, only minimal concentrations of PPIX that are re sponsible for producing side effects can be metabolised in the plasma. Ther efore, no systemic side effects are to be expected after the intravesical a dministration of 5-ALA.