Comparison of sustained-release quinidines given twice daily to patients with ventricular ectopy

To compare the steady-state kinetic profiles and ectopy-suppression rates of two sustained-release forms of quinidine with those of a conventional quinidine preparation, 18 patients with ventricular ectopy were studied in randomized crossover fashion. The drugs were conventional quinidine sulfate 300 mg q6h, sustained-release quinidine sulfate 600 mg q12h, and sustained-release quinidine gluconate 648 mg q12h. Following baseline electrocardiographic ambulatory monitoring, each drug was given for three days, with repeat ambulatory monitoring and serial plasma drug level determinations performed on the third day. There were no washout periods between treatments. Plasma quinidine levels were assayed by both enzyme multiplied immunoassay technique (EMIT) and quinidine-specific high-performance liquid chromatography (HPLC) methods. Using actual steady-state HPLC values, there were no differences in the area under the plasma concentration-time curve (AUC) among the three treatments; the dose-corrected AUC was greater for quinidine gluconate than for the other two preparations. Using EMIT values, mean plasma quinidine levels from the conventional quinidine sulfate regimen were greater during the last five hours of the 12-hour study interval. A consistently strong inverse relationship between EMIT plasma quinidine levels and hourly ectopy rates was present in only one of eight (13%) responders. Diurnal variation of quinidine kinetics was observed after two days of each treatment; trough values at midnight were slightly lower than trough values at noon. Among patients demonstrating at least 70% suppression of premature ventricular contractions (PVCs), there were no differences in ectopy rates or ectopy-suppression rates among treatments. Dosing sustained-release quinidine sulfate 600 mg or quinidine gluconate 648 mg q12h was clinically acceptable in the small number of responders studied.