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.

The pharmacokinetics and pharmacodynamics of quinine in the diabetic and non‐diabetic elderly.

“…Serum free drug concentrations in our series, determined under standardised conditions, were generally higher than those reported by some authors [17,21,24] but not others [ 25,26]. These discrepancies may be due, in part, to differences in sample pH and a,-acid glycoprotein concentrations [19].…”

A quinine a day keeps the leg cramps away?

“…(1975): 6 h in that of Salem et al (1978) and in elderly patients, who were relatively 'drug free' by comparison with those in the present study (7 h, Salem et al (1978)). Berlin et al (1975) also demonstrated that the half-time was dose-dependent, reaching a mean value of 16 h with a six-fold dose increment. The problem of tailoring the dose to the individual becomes even greater when the various oral presentations are considered : Garnham et al (1976) demonstrated that the bioavailability of quinine was dependent not only on the solubility of the salt selected, but also on whether or not the tablets were sugar-coated.…”

Pharmacokinetics of quinine in chronic liver disease.

“…However, quinine is a low hepatic extraction drug [15] which is binding-sensitive and therefore the present changes are likely to result from an alteration in enzyme activity and plasma protein binding of the drug. In plasma, quinine binds to protein, principally to a1-acid glycoprotein (AAG), although approximately 30% binds to albumin [16]. Changes in this acute phase reactant concentrations, and parallel changes in the plasma binding of basic drugs have been reported in several conditions, for example, inflammation, malignancy, stress, nephrotic syndrome, malnutrition and hepatic diseases [17][18].…”