[An experimental model for the rational treatment of arrhythmias: a clinical study with quinidine]

Fourteen patients with supraventricular and/or ventricular ectopic beats selected by clinical, dynamic ECG and exercise test, underwent a basal continuous ECG recording (Holter) and then were given 400 mg of quinidine orally. The concentrations of the drug were determined in blood samples taken 30 minutes before, and 1, 2, 4, 6, 8, 12, and 24 hours after administration. On the same day patients were also monitored by continuous ECG recording (Holter). One week later, after a washout period, the same subjects were treated with 200 mg of quinidine orally 4 times a day for two weeks. On day 1, 2, 4, 7 and 14 quinidine was determined in plasma, and on day 7 and 14 a 24 hour ECG recording was also done. On the basis of pharmacokinetic parameters obtained from the acute test, the chronic levels of the drug were predicted. Predicted values were superimposable to those observed. Thus, the kinetics of single-dose quinidine is able to predict the steady-state levels after repeated dosing. During acute administration there was an increase in QTc interval and a decrease in ectopic beats. These effects correlated with a sigmoid pattern with acute quinidine levels. Concentrations producing 50% of the effect (EC50) could be calculated from these curves. In spite of similar steady-state blood levels of quinidine, some patients after chronic therapy did not respond to treatment (non responders). Non responders could be predicted by the acute test because they had greater EC50 values of QTc increase: patients with EC50 greater than 2 mg/L were all non responders.