Adaptation of the dose of mexiletine according to pharmacokinetic data.

Abstract

Although pharmacodynamic factors are very important in regard to the need for dose adaptation of mexiletine, pharmacokinetic factors also play a role. Pharmacokinetic variability for mexiletine is mainly due to interindividual differences in biotransformation rate in patients with normal hepatic function. Whether the existence of a compromised renal, hepatic or cardiac function alters dosage requirements is not clear. Oral administration of three times 250 mg daily is probably a good starting dose but adaptation will be necessary in many patients. The need for a loading dose depends on the urgency of the situation. For the intravenous administration a loading dose is always necessary. A regimen consisting of 100 to 250 mg mexiletine over 10 minutes, followed by 200 mg over 1 hour has been proposed. This is then followed by a continuous infusion of 0.5-2.5 mg/min. Pharmacodynamic variations notwithstanding, it is of interest to obtain plasma levels of mexiletine within the range of 1-2 microgram/ml.