Vol. 301, Issue 2, 507-512, May 2002

Clinical Pharmacokinetics of 5-Aminolevulinic Acid in Healthy Volunteers and Patients at High Risk for Recurrent Bladder Cancer

James T. Dalton, Charles R. Yates, Donghua Yin, Arthur Straughn, Stuart L. Marcus, Allyn L. Golub and Marvin C. Meyer

Division of Pharmaceutics and Pharmaceutical Chemistry, College of Pharmacy, The Ohio State University, Columbus, Ohio (J.T.D., D.Y.); Department of Pharmaceutical Sciences, College of Pharmacy, University of Tennessee, Memphis, Tennessee (C.R.Y., A.S., M.C.M.); DUSA Pharmaceuticals, Inc., Valhalla, New York (S.L.M.); and Guidelines Integrated Services, Inc., Miramar, Florida (A.L.G.)

5-Aminolevulinic acid (ALA) is a precursor of protoporphyrin IX (PpIX) that is being evaluated for use in photodiagnosis and phototherapy of malignant and nonmalignant disorders. Previous clinical studies using topical, oral, and intravesical administration have been conducted in attempts to determine the optimal route of administration for ALA. The purpose of these studies was to examine the systemic pharmacokinetics and elimination of ALA, the bioavailability of ALA after oral and intravesical doses, and the factors that affect ALA concentrations in the bladder during intravesical treatment. The disposition of ALA was evaluated in six healthy volunteers receiving single intravenous and oral doses (100 mg) and eight patients at high risk for recurrent bladder cancer receiving an intravesical dose (1.328 g) of ALA. The mean (±S.D.) plasma area under the plasma concentration-time curve from time 0 to infinity of PpIX (0.20 ± 0.11 µg · h/ml) after intravenous administration of ALA was not significantly different from that observed after oral administration of ALA (0.15 ± 0.11 µg*h/ml; P = 0.49). ALA terminal half-life was approximately 45 min after intravenous or oral administration. The oral bioavailability of ALA was approximately 60%. After intravesical administration, urine production was largely responsible for decreases in ALA concentration in the bladder, with less than 1% being absorbed into the systemic circulation. In summary, oral and intravenous administration of ALA at these doses results in modest plasma levels of PpIX. Regional administration (i.e., intravesical) of ALA resulted in a significant pharmacokinetic advantage, with urinary bladder being exposed to concentrations approximately 20,000-fold higher than systemic circulation.