ArticlesSingle-Dose Pharmacokinetics of Lamotrigine in Children: Influence of Age and Antiepileptic ComedicationBattino, Dina* ; Croci, Danilo* ; Granata, Tiziana* ; Mamoli, Daniela* ; Messina, Sara†; Perucca, Emilio†Author Information *Carlo Besta Neurological Institute, Milan; and †Clinical Pharmacology Unit, University of Pavia, Pavia, Italy Received October 12, 2000; accepted January 30, 2001. Address correspondence and reprint requests to Dr. Dina Battino, Carlo Besta Neurological Institute, Via Celoria 11, 20133 Milan, Italy. Therapeutic Drug Monitoring: June 2001 - Volume 23 - Issue 3 - p 217-222 Buy Abstract To evaluate the influence of pediatric age and antiepileptic comedication on the single-dose pharmacokinetics of lamotrigine, 19 patients with epilepsy (10 comedicated with enzyme inducers and 9 comedicated with valproic acid) aged 8 months to 30 years received a single oral dose of lamotrigine (0.6 to 2.2 mg/kg) after an overnight fast. Blood samples were collected for at least 36 hours and plasma lamotrigine concentrations were determined by high-performance liquid chromatography. Pharmacokinetic parameters were calculated by noncompartmental analysis. Lamotrigine half-life (T1/2) and oral clearance (Cl/F) values were significantly lower and significantly higher, respectively, in patients comedicated with enzyme inducers than in those receiving valproic acid (T1/2 = 8.1 vs. 41.7 hours respectively, P < 0.001; Cl/F = 0.11 vs. 0.04 L/h per kg respectively, P < 0.005, geometric means), whereas Cmax and Tmax values were comparable in the two groups. The differences in pharmacokinetic parameters persisted when comparisons were made within subgroups stratified according to age. Within groups of patients homogeneous for type of comedication, Cmax and AUC values tended to be lower in children aged less than 12 years than in older patients. There was no significant relationship between half-life values and age. The authors conclude that both age and type of comedication influence lamotrigine pharmacokinetics. The reduction in lamotrigine concentrations caused by enzyme inducers and the elevation caused by valproic acid can be explained by stimulation and inhibition, respectively, of lamotrigine glucuronidation. On the other hand, the lower plasma lamotrigine levels in children than in adolescents and older patients may not be explainable solely by differences in metabolic rate. © 2001 Lippincott Williams & Wilkins, Inc.