D. Battino et al., Single-dose pharmacokinetics of lamotrigine in children: Influence of age and antiepileptic comedication, THER DRUG M, 23(3), 2001, pp. 217-222
To evaluate the influence of pediatric age and antiepileptic comedication o
n the single-dose pharmacokinetics of lamotrigine, 19 patients with epileps
y (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 hi
gh-performance liquid chromatography. Pharmacokinetic parameters were calcu
lated by noncompartmental analysis. Lamotrigine half-life (T-1/2) and oral
clearance (Cl/F) values were significantly lower and significantly higher,
respectively, in patients comedicated with enzyme inducers than in those re
ceiving valproic acid (T-1/2 = 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 C,,, and T,,, values were comparable in the two groups. The differe
nces in pharmacokinetic parameters persisted when comparisons were made wit
hin subgroups stratified according to age. Within groups of patients homoge
neous for type of comedication, C-max and AUC values tended to be lower in
children aged less than 12 years than in older patients. There was no signi
ficant relationship between half-life values and age. The authors conclude
that both age and type of comedication influence lamotrigine pharmacokineti
cs. The reduction in lamotrigine concentrations caused by enzyme inducers a
nd the elevation caused by valproic acid can be explained by stimulation an
d inhibition, respectively, of lamotrigine glucuronidation. On the other ha
nd, the lower plasma lamotrigine levels in children than in adolescents and
older patients may not be explainable solely by differences in metabolic r
ate.