Quinine-induced alterations in drug disposition

Abstract

In normal volunteers, chronic quinine administration shortened plasma antipyrine half-life and significantly increased the intraindividual correlation between the disposition of quinine and antipyrine. Decreased plasma antipyrine half-life appears to be due to a quinine-induced enhancement of antipyrine metabolism. A dose-dependent prolongation of plasma quinine half-life was observed and attributed primarily to an increased apparent volume of distribution of quinine, although our data did not permit separation of an effect on quinine metabolism from an effect on quinine distribution between the peripheral and central compartments. Plasma protein binding of quinine was similar at both the low and high doses of quinine. Studies in dogs given quinine intravenously revealed a biphasic plasma decay curve compatible with a 2-compartment open model for quinine disposition. Dose dependence of plasma quinine half-life in the dog after intravenous quinine eliminated altered gastrointestinal absorption of quinine as a cause for the dose dependence of plasma quinine half-life. These studies illustrate the importance of such conditions as dose and time of administration in determining the type and magnitude of interaction observed between drugs.