Flavone acetic acid: a nonlinear pharmacokinetic model

✍ Scribed by Alain Gouyette; David J. Kerr; Stan B. Kaye; Albert Setanoians; James Cassidy; Christopher Bradley; Gordon Forrest; Mike Soukop

• Book ID: 104687117
• Publisher: Springer
• Year: 1988
• Tongue: English
• Weight: 469 KB
• Volume: 22
• Category: Article
• ISSN: 0344-5704
• DOI: 10.1007/bf00257307

✦ Synopsis

Flavone acetic acid pharmacokinetics were studied in 31 patients in a phase I clinical trial. The drug was given by i.v. infusions over 1, 1.5, 3, and 6 h at doses ranging from 0.5 to 6.4 g/m2. The pharmacokinetic parameters were determined according to a nonlinear model including Michaelis-Menten-type kinetics. The mean elimination half-life is 4.8 h and the mean volume of distribution of the central compartment, 7.61. Our model predicted a maximal tolerated dose (MTD) of 11.1 g/m2 on the basis of the "therapeutic window" concept, very close to the clinically observed MTD of 10 g/m2. This model is also operational when different protocols of inoculation are considered, such as a divided-dose schedule vs a unique infusion, and indicates that, at the MTD, injections should be made every 72 h to avoid drug accumulation.