Cibenzoline is a newly developed antiarrhythmic drug which possesses a local anesthetic action. We studied the pharmacokinetics of cibenzoline and its effects on ventricular premature contractions (VPCs) in 27 patients by a single oral administration method.Blood samples were drawn before and at 0. 5, 1, 2, 3, 4, 6, 8, 12, 24, 36, and 48 hr after the drug administration (4 mg/kg) to measure the plasma drug concentration using high performance liquid chromatography (HPLC). A standard 12-lead ECG was recorded at the time of blood sampling to evaluate the effects of cibenzoline on electrocardiographic parameters and a 24-hr dynamic ECG was also obtained on the day before and after the drug administration to assess the suppressive effects on VPCs. Tmax. was 2.9±1.5 hr in 23 patients with normal renal function (group A) and 3. 1±1. 5 hr in 4 with renal dysfunc tion (group B). Cmax was 596±228 ng/ml for group A and 739±134 ng/ml for group B. T1/2β was 10. 1±5.1 hr for group A and 13. 5±1. 8 hr for group B, and AUC was 5, 880± 2, 334ng/ml·hr for group A and 11, 864±5, 165ng/ml·hr for group B. Urinary excretion rate was 43±16% for group A and 31±20% for group B. Effective suppression of VPCs was found in 17 out of 20 patients who had VPCs of more than 1, 000/24 hr. The average of the minimum effective plasma concentration that was defined as the one showing more than 75% reduction of the baseline frequency of VPCs (beats/hr) was 329±147 ng/ml. RR, PQ and QTc intervals, and QRS duration were prolonged, and blood pressure was slightly elevated after the drug administration. However, there were no serious adverse effects in any patient. These data suggest that 1) pharmacokinetics of cibenzoline strongly depends on the renal function of individual patients, 2) cibenzoline was a safe and highly effective antiarrhythmic drug on VPCs, 3) the drug concentration should be monitored during the maintenance therapy in patients with renal dysfunction.
