高齢者における新しいＣｌａｓｓ Ｉ抗不整脈薬Ｃｉｂｅｎｚｏｌｉｎｅ Ｓｕｃｃｉｎａｔｅの体内動態および有用性について

Abstract

The pharmacokinetic properties and antiarrhythmic effects of cibenzoline, a new class I antiarrhythmic drug, were studied in 12 aged patients (mean age 79 years) with frequent ventricular premature contractions (VPC). A single dose of 1.4 mg/kg of cibenzoline was infused intravenously over two minutes. In 3 patients with a creatinine clearance (Ccr) of less than 40ml/min and in 7 patients with Ccr of 40ml/min or higher, the elimination half-life (t1/2β) was 8.9 hr and 15.4 hr, area under the plasma concentration-time curve (AUC) was 1904ng·hr/ml and 3163 ng·hr/ml, total body clearance (ClT) was 217 ml/min and 447 ml/min, and renal clearance (ClR) was 86ml/min and 145ml/min, respectively. The t1/2β AUC, ClT and ClR showed a close correlation to Ccr. The t1/2β was prolonged, AUC in-creased, and ClT and ClR decreased with decreasing renal function.In 10 out of 12 patients, VPC frequency decreased by more than 90% in 30 minutes after intravenous injection. Therefore, the improvement rate of “markedly or moderately improved” was 83% in the global improvement rating. Side effects observed in 2 patients were as follows: VPC frequency increased in 1 patient and supraventricular premature contraction appeared in 1 patient immediately after intravenous injection. However, these proarrhythmic effects were mild and transient. Cibenzoline significantly prolonged QTc and QRS width. However, cibenzoline showed no effects on R-R and PQ intervals. Though both systolic and diastolic blood pressures were reduced, these reductions were caused by diurnal change.These results suggest that cibenzoline should be used with caution in elderly patients. In particular, in the presence of renal dysfunction, more careful clinical observation seems man datory, since a significant reduction of elimination was noted.