title: Population pharmacokinetics of lamotrigine adjunctive therapy in adults with epilepsy.
abstract: Plasma concentrations of lamotrigine, an antiepileptic drug obtained in three adult controlled clinical trials conducted in the United States were pooled and analyzed using NONMEM, a population pharmacokinetic computer program, to facilitate development of dosing guidelines. A total of 2,407 lamotrigine plasma concentrations from 527 patients with epilepsy were analyzed. Regression equations for oral clearance were developed as a function of body size, age (18-64 years), gender, race, and use of concomitant antiepileptic drugs. The population mean apparent oral clearance of lamotrigine in adult 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 non-whites and increased by 13% in patients receiving more than one concomitant enzyme-inducing antiepileptic agent. Lamotrigine did not influence the disposition of phenytoin or carbamazepine. Dosing adjustments for lamotrigine in patients receiving concomitant enzyme-inducing antiepileptic drugs and not valproic acid should not be necessary for age, gender, or the number of concomitant enzyme-inducing antiepileptic drugs. Lamotrigine does not influence the dosing requirements for phenytoin or carbamazepine.
authors: Pharmaceutical Outcomes Research, Inc., Williamsville, New York, USA.
authors: T H
authors: TH
authors: Grasela
authors: J
authors: J
authors: Fiedler-Kelly
authors: E
authors: E
authors: Cox
authors: G P
authors: GP
authors: Womble
authors: M E
authors: ME
authors: Risner
authors: C
authors: C
authors: Chen
mesh_terms: D000293:Adolescent; D000328:Adult; D000927:Anticonvulsants / Q000493:pharmacokinetics / Q000627:therapeutic use*; D002220:Carbamazepine / Q000627:therapeutic use; D017322:Clinical Trials, Phase II as Topic; D017326:Clinical Trials, Phase III as Topic; D004311:Double-Blind Method; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D004827:Epilepsy / Q000097:blood / Q000188:drug therapy*; D005260:Female; D006801:Humans; D000077213:Lamotrigine; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D010634:Phenobarbital / Q000627:therapeutic use; D010672:Phenytoin / Q000627:therapeutic use; D011324:Primidone / Q000627:therapeutic use; D016032:Randomized Controlled Trials as Topic; D012189:Retrospective Studies; D014227:Triazines / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use*
chemical_list: D000927:Anticonvulsants; D014227:Triazines; D011324:Primidone; D002220:Carbamazepine; D010672:Phenytoin; D000077213:Lamotrigine; D010634:Phenobarbital