Pharmacokinetics of aminolevulinic acid after intravesical administration to dogs

Purpose, To examine the stability and systemic absorption of aminolevulinic acid (ALA) in dogs during intravesical administration. Methods. Nine dogs received an intravesical dose of ALA either with no prio r treatment, after receiving ammonium chloride For urinary acidification, o r after receiving sodium bicarbonate for urinary alkalinization. Urine and blood samples collected during and after administration were monitored for ALA using an HPLC assay developed in our laboratories. Concentrations of py razine 2,5-dipropionic acid, the major ALA degradation product, and radiola beled inulin, a nonabsorbable marker for urine volume, were also determined . Results. Less than 0.6% of intravesical ALA doses was absorbed into plasma. Urine concentrations decreased to 37% of the initial concentration during the 2 hour instillation. Decreases in urinary ALA and radiolabeled inulin c oncentrations were significantly correlated, indicating that urine dilution accounted for over 80% of observed decreases in urinary ALA. ALA conversio n to pyrazine 2,5-dipropionic acid was negligible. Conclusions. These studies demonstrate that ALA is stable and poorly absorb ed into the systemic circulation during intravesical instillation. Future s tudies utilizing intravesical ALA for photodiagnosis of bladder cancer shou ld include measures to restrict fluid intake as a means to limit dilution a nd maximize ALA concentrations during instillation.