4.3 Article

Effect of congestive heart failure on mexiletine pharmacokinetics in a Japanese population

期刊

BIOLOGICAL & PHARMACEUTICAL BULLETIN
卷 29, 期 11, 页码 2267-2269

出版社

PHARMACEUTICAL SOC JAPAN
DOI: 10.1248/bpb.29.2267

关键词

clearance; congestive heart failure; New York Heart Association (NYHA); mexiletine

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Objective: The goal of this study was to evaluate the influence of congestive heart failure (CHF) on the clearance of mexiletine. Methods: The mexiletine clearance/bioavailability (CL/F) ratio was estimated in 584 inpatients receiving mexiletine therapy. The study population consisted of 210 patients with CHF [CHF group; 116 inpatients with New York Heart Association (NYHA) class I-II (group NYHA I-H) CHF and 94 inpatients with NYHA class III-IV (group NYHA III-IV) CHF] and 374 inpatients without CHF (Non-CHF group). Serum levels of mexiletine were determined by high performance liquid chromatography (HPLC). Results: Mexiletine clearance was significantly lower in the CHIT group when compared with the Non-CHF group (0.264 +/- 0.093 vs. 0.3931 +/- 0.0821/h/kg, mean +/- S.D., p < 0.05). Further, the CL/F ratio was 50% lower in group NYHA III-IV when compared with the Non-CHF group, and the CL/F ratio tended to change in inverse proportion to NYHA class. Conclusion: CHF status significantly affects mexiletine clearance. Therefore, dose adjustments and careful monitoring are likely required in CHF patients receiving mexiletine.

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