EFFECT OF GRAPEFRUIT JUICE ON THE PHARMACOKINETICS AND PHARMACODYNAMICS OF QUINIDINE IN HEALTHY-VOLUNTEERS

A study was conducted to examine the effect of grapefruit juice on the disposition of quinidine sulfate and changes of QT intervals after or al administration to twelve healthy male volunteers. Participants rece ived true oral doses of quinidine sulfate tablets (400 mg) with 240 mt of water or grapefruit juice, each separated by a 1-week washout peri od. Plasma samples for analysis of quinidine and its major metabolite, 3-hydroxyquinidine, were collected for a 24-hour period and analyzed by a high performance liquid chromatography method. For pharmacodynami c data, the electrocardiograms (ECGs) were performed for 12 hours, and the recordings were marked for ECG interval at all blood collection t ime periods. There was no significant difference in pharmacokinetic pa rameters of quinidine when administered with grapefruit juice or water , except for time to maximum concentration (t(max)), which was 1.6 hou rs after administration with water and 3.3 hours after administration with grapefruit juice. Administration with grapefruit juice also resul ted in a 33% decrease in the area under the concentration-time curve ( AUC) of 3-hydroxyquinidine compared with water, but did not increase t he AUC of quinidine or change the ratio of AUC of 3-hydroxyquinidine t o the AUC of quinidine. Pharmacodynamic parameters, including changes in the rate-corrected QT (QTc) interval, closely paralleled the pharma cokinetic data, in that administration with grapefruit juice led to de layed maximal effect on QTc and reduction in maximal effect. Administr ation with grapefruit juice therefore delays the absorption of quinidi ne and inhibits the metabolism of quinidine to 3-hydroxyquinidine.