Pharmacokinetics and nondialyzability of mexiletine in renal failure

Mexiletine is an investigational antiarrhythmic drug eliminated primarily by hepatic metabolism. To evaluate its pharmacokinetics in patients with renal failure, we gave 14 subjects (creatinine clearance from 0 to 68.9 ml/min, including five subjects who required maintenance dialysis) a single, 200 mg dose of mexiletine. Serial blood samples were drawn and analyzed for mexiletine concentration by gas chromatography. The elimination t1/2 was 18.9 +/- 7.4 hours and oral clearance was 378 +/- 109 ml/min (means +/- SD). There was no correlation between these parameters and creatinine clearance. In subjects receiving dialysis, the study was also repeated during dialysis 1 week later. There was no significant difference between the AUCs either while receiving dialysis or when calculated on a day when the subject was not receiving dialysis. Thus dosing adjustments for mexiletine should not be necessary in patients with creatinine clearance values as low as 10 ml/min or in patients receiving dialysis. Furthermore, supplemental doses of mexiletine are not likely to be needed after dialysis. Evaluation of the kinetics at steady state are necessary to extrapolate further our observations after a single oral dose.