Pharmacokinetics of mexiletine in renal insufficiency

Mexiletine (Mexitil) is an effective antiarrhythmic drug for the treatment of ventricular dysrhythmias. The therapeutic plasma level is situated between 0.75 and 2 microgram/ml. For concentrations higher than 2 microgram/ml, the percentage of severe side effects is rapidly increasing without improvement of the therapeutic efficacy. The main pharmacokinetics parameters of mexiletine are reviewed in the first part of this publication. Contrary to lidocaine, mexiletine may be administrated orally (or intravenously). It is largely and rapidly distributed in the body. The apparent volume of distribution (Vd) is greater than 500 1. The plasma half-time is 10 to 12 hours in healthy volunteers with a 70% plasma protein fixation. Mexiletine is largely metabolized to conjugates after N-methylation and hydroxylation. In the second part of the work, the influence of renal insufficiency on the plasma half-time of mexiletine has been investigated in 11 patients presenting a creatinine clearance situated between 2 and 38 ml/min. The mean plasma half-time for these patients is 11.1 +/- 1.7 hours after a single i.v. injection of 1.5 mg/kg. This value is comparable to the normal values found in the literature. Our control group containing convalescents from acute myocardial infarct has a plasma half-time of only 5.9 hours. In conclusion, the renal insufficiency has not modified the plasma elimination half-time of mexiletine after a single i.v. injection.