Increase of mexiletine plasma levels due to delayed hepatic metabolism in patients with chronic liver disease.

The clinical relevance of changes in pharmacokinetics of oral mexiletine (600 mg daily dose) was studied in 82 patients with ventricular arrhythmias and impaired liver, renal or heart function (control group n = 51, patients with liver cirrhosis n = 9, with renal insufficiency n = 14, or heart failure n = 8). Increased plasma levels of mexiletine were found in patients with chronic liver disease (2.21 +/- 0.94 micrograms/ml, versus 0.63 +/- 0.22 micrograms/ml of controls, P less than 0.01). Plasma levels in patients with renal insufficiency or heart failure were not significantly different from the controls. The resulting elevated plasma levels in patients with liver cirrhosis emphasize the importance of hepatic metabolism in the elimination of mexiletine. Drug monitoring must be considered necessary in patients with impaired liver function.