Population pharmacokinetics of lamotrigine adjunctive therapy in adults with epilepsy

Plasma concentrations of lamotrigine, an antiepileptic drug obtained in thr ee adult controlled clinical trials conducted in the United States were poo led and analyzed using NONMEM, a population pharmacokinetic computer progra m, to facilitate development of dosing guidelines. A total of 2,407 lamotri gine-plasma concentrations from 527 patients with epilepsy were analyzed. R egression equations for oral clearance were developed as a function of body size, age (18-64 years), gender, race, and use of concomitant antiepilepti c drugs. The population mean apparent oral clearance of lamotrigine in adul t patients receiving one concomitant enzyme-inducing antiepileptic drug and not valproic acid was estimated to be 1 mL/min/kg. Gender and age did not affect clearance significantly. On average, clearance was reduced by 25% in nonwhites and increased by 13% in patients receiving more than one concomi tant enzyme-inducing antiepileptic agent. Lamotrigine did not influence the disposition of phenytoin or carbamazepine. Dosing adjustments for lamotrig ine in patients receiving concomitant enzyme-inducing antiepileptic drugs a nd not valproic acid should not be necessary for age, gender, or the number of concomitant enzyme-inducing antiepileptic drugs. Lamotrigine does not i nfluence the dosing requirements for phenytoin or carbamazepine. (C) 1999 t he American College of Clinical Pharmacology.