Population pharmacokinetics of lamotrigine

Chan, V., Morris, R. G., Ilett, K. F. and Tett, S. E. (2001) Population pharmacokinetics of lamotrigine. Therapeutic Drug Monitoring, 23 6: 630-635. doi:10.1097/00007691-200112000-00006


Author Chan, V.
Morris, R. G.
Ilett, K. F.
Tett, S. E.
Title Population pharmacokinetics of lamotrigine
Journal name Therapeutic Drug Monitoring   Check publisher's open access policy
ISSN 0163-4356
Publication date 2001
Sub-type Article (original research)
DOI 10.1097/00007691-200112000-00006
Volume 23
Issue 6
Start page 630
End page 635
Total pages 6
Editor S. J. Soldin
F. Sjoqvist
Place of publication Philadelphia
Publisher Lippincott & Wilkins
Collection year 2001
Language eng
Subject C1
320502 Basic Pharmacology
730199 Clinical health not specific to particular organs, diseases and conditions
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 spare 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 (TM) (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.
Keyword Medical Laboratory Technology
Pharmacology & Pharmacy
Toxicology
Lamotrigine
Population Pharmacokinetics
Epilepsy
Clearance
Antiepileptic Drugs
Epileptic Patients
Therapy
Valproate
Children
Efficacy
Adults
Age
Q-Index Code C1

Document type: Journal Article
Sub-type: Article (original research)
Collection: School of Pharmacy Publications
 
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Created: Tue, 14 Aug 2007, 15:51:19 EST