An investigation of the influence of patient-related factors and comedications on lamotrigine clearance in patients with epilepsy

Lamotrigine (LTG) is one of the most widely used antiepileptic drugs. Confusion still exists in the literature as to the relative influence of age, body weight, and concomitant drug therapy on LTG pharmacokinetics. So, the objective of this study is to evaluate the influence of patient-related factors and comedication on LTG apparent oral clearance (CL/F). A therapeutic drug-monitoring database was used to identify steady-state plasma LTG concentrations in 210 patients. LTG CL/F values were calculated for each patient according to the equationCL/F (L/h per kg)=LTG daily dose (mg/kg)/C-ss (steady state concentration) (mg/L)x24h. A linear-regression model was used to assess the influence of gender, dose, age, and body weight in LTG CL/F. The influence of comedication on LTG CL/F was investigated by applying the Bonferroni post-test. The lowest LTG CL/F was found in patients comedicated with valproate (VPA) (mean, 0.0183L/h per kg), followed by patients receiving VPA+ enzyme inducers (0.0271L/h per kg), patients on LTG monotherapy (0.0298L/h per kg) and patients comedicated with enzyme inducers (0.056L/h per kg) LTG CL/F correlated significantly with LTG dose (P<0.01), but showed no significant relationship with gender, weight, and age. LTG CL/F is influenced by the type of antiepileptic comedication. The correlation with dose may be a spurious finding related to the fact that physicians, in adjusting dosage according to clinical response, are more likely to use larger doses in patients with high clearance values

Analysis of lamotrigine and its metabolites in human plasma and urine by micellar electrokinetic capillary chromatography

A reliable micellar electrokinetic capillary chromatographic method was developed and validated for the determination of lamotrigine and its metabolites in human plasma and urine. The variation of different parameters such as pH of the BGE and SDS concentration were evaluated in order to find optimal conditions. Best separation of the analyses was achieved at pH 9.5, 10 mM borate and 50 mM sodium dodecyl sulfate; melatonin was selected as the internal standard. Isolation of lamotrigine and its metabolites from plasma and urine was accomplished with an original solid-phase extraction procedure using hydrophilic lypophilic balance cartridges. Good absolute recovery of the analytes and satisfactory precision was obtained. The calibration plots for lamotrigine and its metabolites were linear over the 1 \u2013 20 \ub5g/mL concentration ranges. Sensitivity was satisfactory; in fact, the limit of detection and the limit of quantitation of lamotrigine are 500 ng/mL and 1 \ub5g/mL, respectively. The application of the method to real plasma samples from epileptic patients under therapy with lamotrigine gave satisfactory results (in terms of accuracy and selectivity) and in agree with those obtained with a HPLC method