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Population Pharmacokinetics of Lamotrigine Adjunctive Therapy in Adults with Epilepsy
Author(s) -
Grasela Thaddeus H.,
FiedlerKelly Jill,
Cox Eugène,
Womble Gilda P.,
Risner Marcus E.,
Chen Chao
Publication year - 1999
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1177/00912709922007949
Subject(s) - lamotrigine , carbamazepine , anticonvulsant , concomitant , phenytoin , epilepsy , pharmacokinetics , medicine , dosing , population , pharmacology , valproic acid , nonmem , psychiatry , environmental health
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 nonwhites 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.