Flavone acetic acid: a nonlinear pharmacokinetic model |
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Authors: | Alain Gouyette David J. Kerr Stan B. Kaye Albert Setanoians James Cassidy Christopher Bradley Gordon Forrest Mike Soukop |
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Affiliation: | (1) Clinical Pharmacology Unit (UA147 CNRS and U140 INSERM), Institut Gustave-Roussy, Villejuif, France;(2) Department of Medical Oncology, University of Glasgow, UK;(3) Department of Medical Oncology, Glasgow Royal Infirmary, Glasgow, UK;(4) Pavillon de Recherche, Institut Gustave-Roussy, 39, Rue Camille-Desmoulins, F-94805 Villejuif Cedex, France |
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Abstract: | Summary 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. |
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