Kotake Takeshi, Takada Mitsutaka, Komamura Kazuo, Kamakura Shiro, Miyatake Kunio, Kitakaze Masafumi, Morishita Hideki
Department of Pharmacy, National Cardiovascular Center, Suita, Japan.
Circ J. 2006 May;70(5):588-92. doi: 10.1253/circj.70.588.
Cibenzoline dosing is generally based on renal function, but serum concentrations might be greater than the expected therapeutic levels when standard oral dosing is used. Because heart failure might modify cibenzoline pharmacokinetics, the difference in cibenzoline pharmacokinetics between patients with and without heart failure was evaluated.
The study enrolled 368 patients (233 men, 135 women) that had been hospitalized and received cibenzoline therapy at the National Cardiovascular Center from January 2001 to May 2005. There were 89 patients with heart failure (51 men, 38 women) and 279 patients without heart failure (182 men, 97 women). They had therapeutic drug monitoring > or = 3 days after the beginning of treatment with cibenzoline. Brain natriuretic peptide (BNP) was measured in 81 patients (50 men, 31 women) concurrently with therapeutic drug monitoring of cibenzoline. The difference in serum cibenzoline concentration/(dose/weight) (C/D) values between patients with and without heart failure was analyzed using analysis of covariance (ANCOVA) with creatinine clearance (Ccr) serving as the covariate. The effects of dose/weight and the log-transformed BNP (log-BNP) values on serum cibenzoline concentrations were also assessed using ANCOVA. There were 135 and 361 measurements of serum cibenzoline concentration in patients with and without heart failure, respectively. Pearson's correlation coefficient analyses in the patients with and without heart failure revealed that the C/D values were significantly correlated with Ccr (with heart failure, y = -0.837x + 169, r = -0.211, p = 0.014; without heart failure, y = -0.789x + 132, r = -0.393, p < 0.001), and the ANCOVA model indicated that C/D values were significantly higher in patients with heart failure than without heart failure. The ANCOVA model also showed that dose/weight, Ccr and the log-BNP value were significant factors.
The selection of a cibenzoline dose based only on renal function may increase the risk of toxicity in patients with heart failure. Cardiac function should be taken into account in cibenzoline dosing. The log-BNP may be a useful index for predicting serum cibenzoline concentrations.
西苯唑啉的给药剂量通常基于肾功能，但使用标准口服给药时，血清浓度可能高于预期治疗水平。由于心力衰竭可能改变西苯唑啉的药代动力学，因此评估了心力衰竭患者与无心力衰竭患者之间西苯唑啉药代动力学的差异。
该研究纳入了2001年1月至2005年5月期间在国立心血管中心住院并接受西苯唑啉治疗的368例患者（233例男性，135例女性）。其中有89例心力衰竭患者（51例男性，38例女性）和279例无心力衰竭患者（182例男性，97例女性）。他们在开始使用西苯唑啉治疗后3天及以上进行了治疗药物监测。在81例患者（50例男性，31例女性）中同时测定了脑钠肽（BNP）与西苯唑啉的治疗药物监测。以肌酐清除率（Ccr）作为协变量，采用协方差分析（ANCOVA）分析心力衰竭患者与无心力衰竭患者之间血清西苯唑啉浓度/（剂量/体重）（C/D）值的差异。还使用ANCOVA评估了剂量/体重和对数转换后的BNP（log-BNP）值对血清西苯唑啉浓度的影响。心力衰竭患者和无心力衰竭患者的血清西苯唑啉浓度测量值分别为135次和361次。心力衰竭患者和无心力衰竭患者的Pearson相关系数分析显示，C/D值与Ccr显著相关（心力衰竭患者，y = -0.837x + 169，r = -0.211，p = 0.014；无心力衰竭患者，y = -0.789x + 132，r = -0.393，p < 0.001），ANCOVA模型表明心力衰竭患者的C/D值显著高于无心力衰竭患者。ANCOVA模型还显示剂量/体重、Ccr和log-BNP值是显著因素。
仅根据肾功能选择西苯唑啉剂量可能会增加心力衰竭患者的毒性风险。西苯唑啉给药时应考虑心功能。Log-BNP可能是预测血清西苯唑啉浓度的有用指标。
