Dose-dependent pharmacokinetics of flavone acetic acid in mice

Giovanna Damia, Maria Luisa Zanette, Cosmo Rossi, Rosella Mandelli, Aurora Ferrari, Maurizio D'Incalci

Research output: Contribution to journalArticle

Abstract

The pharmacokinetics of the novel anticancer agent, flavone acetic acid (FAA) were investigated in Balb-c mice treated with i. v. doses of 100 mg/kg or 300 mg/kg, using an HPLC assay. The kinetics of disappearance from plasma was monoexponential and dose-dependent. After 100 mg/kg, the plasma peak level was 250±11 μg/ml, t1/2 was 0.5 h, and AUC was 309 μg/ml per h. After 300 mg/kg, the plasma peak level was 710±57 μg/ml, t1/2 was 2.1 h, and the area under the curve (AUC) 1771 μg/ml h. Mouse plasma protein binding of FAA was about 70%. As is the case with plasma, in all tissues analyzed, the FAA-AUC values were disproportinately greater after 300 mg/kg than after 100 mg/kg. The highest drug concentrations were found in the liver and small intestine; concentrations were intermediate in lung, heart, and spleen, and lowest in brain. Less than 5% of the FAA dose was eliminated as unchanged drug in the stool. Total excretion of FAA as unchanged drug in the urine collected up to 96 h after drug treatment corresponded to 75% and 60% of the i. v. doses of 100 and 300 mg/kg, respectively. A minor fraction of FAA dose, corresponding to 1% and 6% of the two doses, was eliminated in the urine as a FAA glucuronide or sulfate.

Original languageEnglish
Pages (from-to)47-50
Number of pages4
JournalCancer Chemotherapy and Pharmacology
Volume22
Issue number1
DOIs
Publication statusPublished - Jul 1988

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ASJC Scopus subject areas

  • Pharmacology
  • Oncology
  • Cancer Research

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