PHASE-I AND CLINICAL-PHARMACOLOGY STUDY OF INTRAVENOUS FLAVONE ACETIC-ACID (NSC-347512)

  • 15 October 1988
    • journal article
    • research article
    • Vol. 48  (20) , 5878-5882
Abstract
We have conducted a Pase I and pharmacological study of flavoneacetic acid, one 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 .mu.g/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 flavoneacetic acid dose was recovered as intact drug and an additional 37% was recovered as a metabolite. The maximally tolerated dose determined this study is 6400 mg/m2 given i.v. over 3 h.