Effect of eslicarbazepine acetate on the pharmacokinetics of metformin in healthy subjects.
OBJECTIVE
Eslicarbazepine acetate (ESL) is a new voltage-gated sodium channel blocker currently in development for the treatment of neuropathic pain, including that of diabetic origin. The primary objective was to investigate the effect of ESL on the pharmacokinetics of metformin, a commonly used oral antidiabetic drug.


METHODS
Randomized, open-label, two-way crossover study in 20 healthy subjects. The volunteers received an 850 mg single-dose of metformin hydrochloride on two occasions - once as such and once after pre-treatment with an oral once-daily dose of ESL 1200 mg for 6 days - separated by a washout period of at least 2 weeks. The bioequivalence approach was used for assessing the effect of ESL on the pharmacokinetics of metformin. Test/Reference geometric mean ratios (GMR) and 90% confidence intervals (90% CI) were calculated for AUC0- yen, AUC0-12 and Cmax of metformin.


RESULTS
Test/Reference metformin GMR (90% CI) was 0.95 (0.86; 1.05) for AUC0- yen, 0.95 (0.88; 1.06) for AUC0-12, and 0.88 (0.77; 1.00) for Cmax. Formal bioequivalence could not be demonstrated for metformin Cmax. However, the extent of exposure to metformin, as reflected by AUC0-12 and AUC0- yen, allows the claim of bioequivalence since the 90% CI of the GMR fall within the pre-specified bioequivalence acceptance interval (0.80; 1.25).


CONCLUSIONS
Once-daily administration of ESL 1,200 mg had no relevant effect on the systemic exposure to metformin pharmacokinetics in healthy subjects.
Rocha
J-F
JF
Department of Research and Development, BIAL, S. Mamede do Coronado, Portugal.
Vaz-da-Silva
M
M
Almeida
L
L
Falcão
A
A
Nunes
T
T
Santos
A-T
AT
Martins
F
F
Fontes-Ribeiro
C
C
Macedo
T
T
Soares-da-Silva
P
P
D000284:Administration, Oral; D000328:Adult; D019540:Area Under Curve; D018592:Cross-Over Studies; D003984:Dibenzazepines / Q000009:adverse effects / Q000494:pharmacology*; D004347:Drug Interactions; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000009:adverse effects / Q000493:pharmacokinetics*; D008297:Male; D008687:Metformin / Q000009:adverse effects / Q000493:pharmacokinetics*; D026941:Sodium Channel Blockers / Q000009:adverse effects / Q000494:pharmacology*; D055815:Young Adult
D003984:Dibenzazepines; D007004:Hypoglycemic Agents; D026941:Sodium Channel Blockers; D008687:Metformin; C416835:eslicarbazepine acetate