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

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.