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.


CONCLUSIONS
CHF status significantly affects mexiletine clearance. Therefore, dose adjustments and careful monitoring are likely required in CHF patients receiving mexiletine.
Kobayashi
Mariko
M
Department of Pharmaceutical Sciences, Niigata University of Pharmacy and Applied Life Sciences, Japan.
Fukumoto
Kyoko
K
Ueno
Kazuyuki
K
D000284:Administration, Oral; D000889:Anti-Arrhythmia Agents / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use; D044466:Asian People; D001682:Biological Availability; D002851:Chromatography, High Pressure Liquid; D004334:Drug Administration Schedule; D016903:Drug Monitoring / Q000379:methods; D005260:Female; D006333:Heart Failure / Q000188:drug therapy* / Q000378:metabolism*; D006801:Humans; D007297:Inpatients; D008297:Male; D008657:Metabolic Clearance Rate; D008801:Mexiletine / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D012720:Severity of Illness Index
D000889:Anti-Arrhythmia Agents; D008801:Mexiletine