Adaptation of the dose of mexiletine according to pharmacokinetic data.

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.