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-II) 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 CHF group when compared with the Non-CHF group (0.264+/-0.093 vs. 0.393+/-0.082 l/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.
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-II) 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 CHF group when compared with the Non-CHF group (0.264+/-0.093 vs. 0.393+/-0.082 l/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 CHFpatients receiving mexiletine.