Clinical pharmacokinetics of 5-aminolevulinic acid in healthy volunteers and patients at high risk for recurrent bladder cancer

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

Research output: Contribution to journalArticle

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Abstract

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 μ*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.

Original languageEnglish (US)
Pages (from-to)507-512
Number of pages6
JournalJournal of Pharmacology and Experimental Therapeutics
Volume301
Issue number2
DOIs
StatePublished - May 4 2002

Fingerprint

Aminolevulinic Acid
Urinary Bladder Neoplasms
Healthy Volunteers
Pharmacokinetics
Intravesical Administration
Oral Administration
Intravenous Administration
Urinary Bladder
Biological Availability
Topical Administration
Phototherapy
Half-Life

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Pharmacology

Cite this

Clinical pharmacokinetics of 5-aminolevulinic acid in healthy volunteers and patients at high risk for recurrent bladder cancer. / Dalton, James T.; Yates, Charles; Yin, Donghua; Straughn, Arthur; Marcus, Stuart L.; Golub, Allyn L.; Meyer, Marvin C.

In: Journal of Pharmacology and Experimental Therapeutics, Vol. 301, No. 2, 04.05.2002, p. 507-512.

Research output: Contribution to journalArticle

Dalton, James T. ; Yates, Charles ; Yin, Donghua ; Straughn, Arthur ; Marcus, Stuart L. ; Golub, Allyn L. ; Meyer, Marvin C. / Clinical pharmacokinetics of 5-aminolevulinic acid in healthy volunteers and patients at high risk for recurrent bladder cancer. In: Journal of Pharmacology and Experimental Therapeutics. 2002 ; Vol. 301, No. 2. pp. 507-512.
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