Please use this identifier to cite or link to this item: http://hdl.handle.net/2440/14566
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Type: Journal article
Title: Population pharmacokinetics of lamotrigine
Author: Chan, V.
Morris, R.
Ilet, K.
Tett, S.
Citation: Therapeutic Drug Monitoring, 2001; 23(6):630-635
Publisher: Lippincott Williams & Wilkins
Issue Date: 2001
ISSN: 0163-4356
1536-3694
Abstract: The present study estimated the population pharmacokinetics of lamotrigine in patients receiving oral lamotrigine therapy with drug concentration monitoring, and determined intersubject and intrasubject variability. A total of 129 patients were analyzed from two clinical sites. Of these, 124 patients provided sparse data (198 concentration-time points); nine patients (four from a previous group plus five from the current group) provided rich data (431 points). The population analysis was conducted using P-PHARM (SIMED Scientific Software, Cedex, France), a nonlinear mixed-effect modeling program. A single exponential elimination model (first-order absorption) with heteroscedastic weighting was used. Apparent clearance (CL/F) and volume of distribution (V/F) were the pharmacokinetic parameters estimated. Covariate analysis was performed to determine which factors explained any of the variability associated with lamotrigine clearance. Population estimates of CL/F and V/F for lamotrigine generated in the final model were 2.14 +/- 0.81 L/h and 78.1 +/- 5.1 L/kg. Intersubject and intrasubject variability for clearance was 38% and 38%, respectively. The covariates of concomitant valproate and phenytoin therapy accounted for 42% of the intersubject variability of clearance. Age, gender, clinic site, and other concomitant antiepileptic drugs did not influence clearance. This study of the population pharmacokinetics of lamotrigine in patients using the drug clinically provides useful data and should lead to better dosage individualization for lamotrigine.
Keywords: Humans; Valproic Acid; Triazines; Anticonvulsants; Metabolic Clearance Rate; Drug Interactions; Adolescent; Adult; Aged; Middle Aged; Female; Male; Lamotrigine
RMID: 0020010790
DOI: 10.1097/00007691-200112000-00006
Appears in Collections:Pharmacology publications

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