Abstract
The purpose of these studies was to examine the pharmacokinetics, oral bioavailability, and systemic side effects of aminolevulinic acid (ALA) in beagle dogs after oral and i.v. administration. Oral and i.v. doses of ALA (128 mg of ALA hydrochloride, equivalent to 100 mg of ALA) were administered to four animals using a crossover design. Animals were allowed a 2-week washout period between doses. Plasma ALA concentrations were determined using precolumn fluorescent derivatization and reversed-phase HPLC. Plasma concentrations after i.v. administration declined rapidly with a terminal half-life of 19.5 ± 2.5 min (mean ± S.D.). Total body clearance and volume of distribution at steady state averaged 6.79 ± 1.77 ml/min/kg and 259 ± 128 ml/kg, respectively. Peak plasma concentrations of ALA after oral administration ranged from 1.27 to 9.42 μg/ml. Oral bioavailability in these animals averaged 41.2 ± 14.8% (range, 23.5–58.5%). These studies demonstrate that oral administration may provide a convenient and efficient route of delivery of ALA for photodynamic therapy in patients.
Footnotes
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Send reprint requests to: James T. Dalton, Ph.D., Department of Pharmaceutical Sciences, University of Tennessee, Memphis, 874 Union Avenue, Crowe Building, Room 5, Memphis, TN 38163. E-mail: jdalton{at}utmem1.utmem.edu
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These studies were supported by a grant from DUSA Pharmaceuticals, Inc. (Valhalla, NY).
- Abbreviations used are::
- PDT
- photodynamic therapy
- ALA
- aminolevulinic acid
- PpIX
- protoporphyrin IX
- Tmax
- time to reach maximum plasma concentration
- Vdss
- volume of distribution at steady state
- CL
- total plasma clearance
- AUC
- area under the plasma concentration-time curve
- Received September 8, 1998.
- Accepted December 18, 1998.
- The American Society for Pharmacology and Experimental Therapeutics
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