| Heart failure elevates serum levels of cibenzoline in arrhythmic patients. | |
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MedLine Citation:
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PMID: 16636495 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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 > 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. 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. |
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Authors:
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Takeshi Kotake; Mitsutaka Takada; Kazuo Komamura; Shiro Kamakura; Kunio Miyatake; Masafumi Kitakaze; Hideki Morishita |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Circulation journal : official journal of the Japanese Circulation Society Volume: 70 ISSN: 1346-9843 ISO Abbreviation: Circ. J. Publication Date: 2006 May |
Date Detail:
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Created Date: 2006-04-25 Completed Date: 2006-07-31 Revised Date: 2007-11-15 |
Medline Journal Info:
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Nlm Unique ID: 101137683 Medline TA: Circ J Country: Japan |
Other Details:
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Languages: eng Pagination: 588-92 Citation Subset: IM |
Affiliation:
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Department of Pharmacy, National Cardiovascular Center, Suita, Japan. kotaket@hsp.ncvc.go.jp |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Adult Aged Aged, 80 and over Anti-Arrhythmia Agents / administration & dosage, blood, pharmacokinetics Body Weight Drug Evaluation Female Heart Failure / drug therapy* Heart Function Tests Humans Imidazoles / administration & dosage*, blood*, pharmacokinetics Kidney Function Tests Male Middle Aged Retrospective Studies |
| Chemical | |
Reg. No./Substance:
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0/Anti-Arrhythmia Agents; 0/Imidazoles; 53267-01-9/cifenline |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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