Heart Failure Elevates Serum Levels of Cibenzoline in Arrhythmic Patients(CLINICAL INVESTIGATION)

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• Background 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. Methods and Results 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 ≥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. Conclusions 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.

• 社団法人日本循環器学会の論文
• 2006-04-20

著者

• KITAKAZE Masafumi

  Division of Cardiology, National Cardiovascular Center

• Kamakura Shiro

  Division of Cardiology, National Cardiovascular Center

• Kosugi Takayoshi

  Department Of Pharmacy National Cardiovascular Center

• Kosugi Takayoshi

  東邦大学医学部附属大森病院 薬剤

• Miyashita K

  Department Of Cardiovascular Surgery National Cardiovascular Center

• Kurita Takashi

  Division Of Cardiology Department Of Internal Medicine National Cardiovascular Center

• Kobayashi Takashi

  Icd Committee Of The Japanese Heart Rhythm Society

• KOMAMURA Kazuo

  Division of Cardiology, National Cardiovascular Center

• KOTAKE Takeshi

  Department of Pharmacy, National Cardiovascular Center

• MORISHITA Hideki

  Department of Pharmacy, National Cardiovascular Center

• Morishita Hideki

  Departments Of Pharmacy National Cardiovascular Center

• Kitakaze Masafumi

  Division Of Cardiology National Cardiovascular Center

• Kitakaze Masafumi

  Nagoya University Graduate School Of Medicine

• Kurose K

  Department Of Vascular Physiology Research Institute National Cardiovascular Center

• Kotake Takeshi

  国立循環器病センター 薬剤部

• Kubo Takashi

  Project Team For Pharmacogenetics National Institute Of Health Sciences

• Kotake Takeshi

  国立医薬品食品衛生研究所

• Komamura K

  国立循環器病センター 心臓血管内科

• Muro K

  国立がんセンター中央病院

• Muro Kei

  Gastrointestinal Oncology Division National Cancer Center Hospital

• Miyatake Kunio

  Department Of Cardiovascular Surgery National Cardiovascular Center

• Miyatake Kunio

  Division of Cardiology, Department of Internal Medicine, National Cardiovascular Center

• Miyashita K

  National Cardiovascular Center

• Miyatake Kunio

  国立病院機構大阪南医療センター 循環器科

• MINATOYA Kenji

  National Cardiovascular Center

• Takada Mitsutaka

  Department of Pharmacy, Research Institute, National Cardiovascular Center

• Matsuura Kaoru

  国立循環器病センター

• Miyatake Kunio

  Hiroshima General Hospital

• Kimura Kohji

  Departments Of Radiology National Cardiovascular Center

• Takada Mitsutaka

  Division Of Practical Pharmacy Faculty Of Pharmaceutical Sciences Kinki University

• Takada Mitsutaka

  Division Of Practical Pharmacy School Of Pharmaceutical Sciences Kinki University Osakasayama

• Miyashita Kotaro

  Department Of Cardiology National Cardiovascular Center

• Kajikawa Mariko

  ABLE Corporation

• Miyatake Kunio

  Department Of Cardiology National Cardiovascular Center

• Miyatake Kunio

  National Hospital Organization Osaka Minami Medical Center

• Manabe Kasumi

  Division Of Cardiovascular Medicine National Cardiovascular Center

• Kusumoto Miyako

  Cardiac Division National Cardiovascular Center

• Kawamoto Toshihiro

  Department Of Environmental Health School Of Medicine University Of Occupational And Environmental H

• Miyashita Kotaro

  National Cardiovascular Center Department Of Cerebrovascular Medicine

• Morishita Hideki

  Department Of Pharmacy National Cardiovascular Center

• Miyatake Kunio

  Division Of Cardiology Department Of Medicine National Cardiovascular Center

• Kamakura Shiro

  Division Of Cardiology Department Of Internal Medicine National Cardiovascular Center

• Motegi Katsuhiko

  Division Of Cardiology Department Of Internal Medicine And Division Of Cardiac Sugery

• Komamura Kazuo

  Division Of Cardiology National Cardiovascular Center

• Kamakura Shiro

  Division Of Arrhythmia And Electrophysiology Department Of Cardiovascular Medicine National Cerebral

• Miyatake Kunio

  Devision Of Cardiology National Caediovascular Center

• Maeda Kumiko

  Department Of Medicine Osaka Ekisaikai Hospital

• Miyatake Kunio

  Hospital Osaka

• Miyamoto Koji

  Department Of Cardiology National Cardiovascular Center

• Kotake Takeshi

  Department of Internal Medicine, Toyonaka Municipal Hospital

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