Quinidine Polygalacturonate

This study compared the relative bioavailability characteristics of quinidine polygalacturonate (QP) and quinidine sulfate (QS) after oral administration of commercial tablets and a liquid form prepared from crushed tablets in 13 healthy adult male volunteers. Each subject received the following four single-dose treatments in a randomized, crossover manner with a one-week washout period between treatments: 400 mg QS liquid, two 200-mg QS tablets, 550 mg QP liquid, and two 275-mg QP tablets. All four treatments were equivalent in terms of the dose of quinidine base. Multiple serum samples and two 24-hour urine specimens were collected over 24 and 48 hours, respectively, and assayed for quinidine with a specific HPLC assay method. For the absorption and disposition parameters measured (maximum serum concentration, time to reach maximum concentration, area under the concentration-time curve [0–48 hours], absorption and elimination rate constants, absorption and elimination half-lives, apparent total body clearance, apparent volume of distribution, and dose fraction excreted in the urine) no significant differences were observed for any of the parameters among the four treatments (p>0.05). The results of the present investigation demonstrated that QP and QS produced identical serum quinidine concentration-time curves when given in the form of a tablet or liquid. The clinical implications of these observations with respect to the dosing of QP are discussed.

The Authors report a case of incessant torsade de pointes, associated with QT prolongation, due to the proarrhythmic effect of quinidine, which was successfully treated with i.v. verapamil. The arrhythmia occurred after oral administration of quinidine polygalacturonate (550 mg + 275 mg + 275 mg over a 4-hour period) for the conversion of atrial fibrillation in a 41-year-old woman with mild mitral stenosis and regurgitation. Verapamil was administered as an i.v. bolus (5 mg at a rate of 1 mg/min) and with in four minutes the arrhythmia disappeared. The electrophysiological mechanisms of torsade de pointes and the potential role of Ca+(+)-channel-blocking agents in its treatment are briefly discussed.