Pharmacokinetic interaction study between eslicarbazepine acetate and lamotrigine in healthy subjects.
OBJECTIVE
Anti-epileptic drugs are often used in combination. Both eslicarbazepine (main metabolite of eslicarbazepine acetate, ESL) and lamotrigine undergo conjugation with glucuronic acid, and both eslicarbazepine and its glucuronide and lamotrigine glucuronide undergo extensive renal elimination; therefore, there is a potential for interaction. This study investigated the interaction between ESL and lamotrigine in healthy subjects.


METHODS
Open-label study in two parallel groups of 16 healthy volunteers each. After an 8-day treatment with ESL or lamotrigine, ESL (1200 mg once-daily) and lamotrigine (150 mg once-daily) were co-administered for 19 days. Geometric mean ratios (GMR) and 90% confidence intervals (90% CI) for maximum plasma concentration (C(max)) and area under the plasma concentration-time curve in the dosing interval (AUC(0-24)) were calculated for eslicarbazepine (ESL active metabolite) and lamotrigine.


RESULTS
The C(max) and AUC(0-24) GMR (90% CI) were, respectively, 95% (87-102%) and 96% (91-102%) for eslicarbazepine, and 88% (82-94%) and 86% (81-92%) for lamotrigine. The 90% CI of the C(max) and AUC(0-24) GMR fell within the prespecified acceptance interval (80-125%) both for eslicarbazepine and lamotrigine.


CONCLUSIONS
There was no significant pharmacokinetic interaction between ESL and lamotrigine in healthy subjects. Therefore, no dosage adjustment appears to be usually required in either lamotrigine or ESL when the drugs are co-administered.
Almeida
L
L
Department of Research and Development, BIAL, S Mamede do Coronado, Portugal.
Nunes
T
T
Sicard
E
E
Rocha
J-F
JF
Falcão
A
A
Brunet
J-S
JS
Lefebvre
M
M
Soares-da-Silva
P
P
D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000927:Anticonvulsants / Q000008:administration & dosage / Q000493:pharmacokinetics*; D019540:Area Under Curve; D003984:Dibenzazepines / Q000008:administration & dosage / Q000493:pharmacokinetics*; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D004827:Epilepsy / Q000188:drug therapy; D006801:Humans; D000077213:Lamotrigine; D008297:Male; D008875:Middle Aged; D014227:Triazines / Q000008:administration & dosage / Q000493:pharmacokinetics*; D055815:Young Adult
D000927:Anticonvulsants; D003984:Dibenzazepines; D014227:Triazines; C416835:eslicarbazepine acetate; D000077213:Lamotrigine