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Pharmacokinetics of Aminolevulinic Acid After Intravesical Administration to Dogs

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Abstract

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 prior treatment, after receiving ammonium chloride for urinary acidification, or 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 pyrazine 2,5-dipropionic acid, the major ALA degradation product, and radiolabeled 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 concentrations were significantly correlated, indicating that urine dilution accounted for over 80% of observed decreases in urinary ALA. ALA conversion to pyrazine 2,5-dipropionic acid was negligible.

Conclusions. These studies demonstrate that ALA is stable and poorly absorbed into the systemic circulation during intravesical instillation. Future studies utilizing intravesical ALA for photodiagnosis of bladder cancer should include measures to restrict fluid intake as a means to limit dilution and maximize ALA concentrations during instillation.

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Authors and Affiliations

  1. Department of Pharmaceutical Sciences, College of Pharmacy, University of Tennessee, Memphis, 874 Union Avenue, Crowe Building, Room 5, Memphis, Tennessee, 38163

    James T. Dalton, Diansong Zhou, Arnab Mukherjee, David Young & Marvin C. Meyer

  2. Department of Biostatistics and Epidemiology, College of Medicine, University of Tennessee, Memphis, Tennessee, 38163

    Elizabeth A. Tolley

  3. Guidelines, Inc., Miramar, Florida

    Allyn L. Golub

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  1. James T. Dalton
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  2. Diansong Zhou
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  3. Arnab Mukherjee
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  4. David Young
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  5. Elizabeth A. Tolley
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  6. Allyn L. Golub
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  7. Marvin C. Meyer
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Correspondence to James T. Dalton.

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Dalton, J.T., Zhou, D., Mukherjee, A. et al. Pharmacokinetics of Aminolevulinic Acid After Intravesical Administration to Dogs. Pharm Res 16, 288–295 (1999). https://doi.org/10.1023/A:1018840827910

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