Population pharmacokinetics of lamotrigine

The present study estimated the population pharmacokinetics of lamotrigine in patients receiving oral lamotrigine therapy with drug concentration moni toring, and determined intersubject and intrasubject variability. A total o f 129 patients were analyzed from two clinical sites. Of these, 124 patient s 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) (SIM ED Scientific Software, Cedex, France), a nonlinear mixed-effect modeling p rogram. A single exponential elimination model (first-order absorption) wit h heteroscedastic weighting was used. Apparent clearance (CL/F) and volume of distribution (V/F) were the pharmacokinetic parameters estimated. Covari ate 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 +/- 0.8 1 L/h and 78.1 +/- 5.1 L/kg. Intersubject and intrasubject variability for clearance was 38% and 38%, respectively. The covariates of concomitant valp roate and phenytoin therapy accounted for 42% of the intersubject variabili ty of clearance. Age, gender, clinic site, and other concomitant antiepilep tic drugs did not influence clearance. This study of the population pharmac okinetics of lamotrigine in patients using the drug clinically provides use ful data and should lead to better dosage individualization for lamotrigine .