Effect of Grapefruit Juice on the Pharmacokinetics and Pharmacodynamics of Quinidine in Healthy Volunteers

Abstract

A study was conducted to examine the effect of grapefruit juice on the disposition of quinidine sulfate and changes of QT intervals after oral administration to twelve healthy male volunteers. Participants received two oral doses of quinidine sulfate tablets (400 mg) with 240 mL of water or grapefruit juice, each separated by a 1‐week washout period. 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 pharmacodynamic data, the electrocardiograms (ECGs) were performed for 12 hours, and the recordings were marked for ECG interval at all blood collection time periods. There was no significant difference in pharmacokinetic parameters of quinidine when administered with grapefruit juice or water, except for time to maximum concentration (t_max), which was 1.6 hours after administration with water and 3.3 hours after administration with grapefruit juice. Administration with grapefruit juice also resulted in a 33% decrease in the area under the concentration‐time curve (AUC) of 3‐hydroxyquinidine compared with water, but did not increase the AUC of quinidine or change the ratio of AUC of 3‐hydroxyquinidine to the AUC of quinidine. Pharmacodynamic parameters, including changes in the rate‐corrected QT (QTc) interval, closely paralleled the pharmacokinetic data, in that administration with grapefruit juice led to delayed maximal effect on QTc and reduction in maximal effect. Administration with grapefruit juice therefore delays the absorption of quinidine and inhibits the metabolism of quinidine to 3‐hydroxyquinidine.