title: Phase I and clinical pharmacology study of intravenous flavone acetic acid (NSC 347512).
abstract: We have conducted a Phase I and pharmacological study of flavone acetic acid, one of a series of novel flavonoids. The drug was administered i.v. weekly for 4 weeks, with a 2-week rest and then repeated. Flavone acetic acid was given initially in a 1-h infusion, but at the 3900-mg/m2 dose level, the infusion time was lengthened to 3 h. A total of 31 patients were treated with 9 different dose levels, ranging from 330 to 6400 mg/m2. Dose-limiting toxicity was acute hypotension that began after about one-third of each drug dose had been infused and rarely lasted more than a few minutes after the infusion was discontinued. In addition, subjective fatigue and asthenia causing unacceptable patient discomfort was dose limiting. A significant side effect noted that was not dose limiting was diarrhea during the infusion. This drug exhibited nonlinear pharmacokinetic behavior. Plasma levels exceeded 300 micrograms/ml during the infusion at the maximally tolerated dose. After the infusion ended the principal half-life was about 2 h. In 24-h urine collections 27% of the flavone acetic acid dose was recovered as intact drug and an additional 37% was recovered as a metabolite. The maximally tolerated dose determined in this study is 6400 mg/m2 given i.v. over 3 h.
authors.affiliation: Department of Medicine, Walter Reed Army Medical Center, Washington, DC 20307.
authors.forename: R B
authors.initials: RB
authors.lastname: Weiss
authors.forename: R F
authors.initials: RF
authors.lastname: Greene
authors.forename: R D
authors.initials: RD
authors.lastname: Knight
authors.forename: J M
authors.initials: JM
authors.lastname: Collins
authors.forename: J J
authors.initials: JJ
authors.lastname: Pelosi
authors.forename: A
authors.initials: A
authors.lastname: Sulkes
authors.forename: G A
authors.initials: GA
authors.lastname: Curt
mesh_terms: D000328:Adult; D000368:Aged; D001794:Blood Pressure / Q000187:drug effects; D004341:Drug Evaluation; D005260:Female; D005419:Flavonoids / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology
chemical_list: D005419:Flavonoids; C049328:flavone acetic acid