A Two-Sequence, Four-Period, Crossover, Full-Replicate Study to Demonstrate Bioequivalence of Carbamazepine Extended-Release Tablets in Healthy Subjects under Fasting and Fed Conditions

Abstract

Carbamazepine is a first-line antiepileptic drug (AED) used for the treatment of partial and tonic-clonic seizures. We conducted an open label, balanced, randomized, two-treatment, two-sequence, four-period, single oral dose, full-replicate crossover study to assess and compare the bioequivalence of test product Carbamazepine extended release tablets USP 400 mg with reference product Tegretol®-XR 400 mg (Carbamazepine extended release tablets), respectively in healthy subjects under fasting and fed conditions. Blood samples were collected pre-dose and at regular intervals post-dose up to 240.00 hours. The plasma concentration was analyzed by a validated LC-MS/MS method and the reference-scaled and the unscaled procedure was used to determine bioequivalence for the pharmacokinetics parameters, Cmax, AUC0–t, AUC0-inf, Tmax, T½, Kel and AUC extrapolated was calculated. The results showed that the geometric mean ratios of Cmax, AUC0–t and AUC0-inf were 113.04%, 108.33% and 108.15% respectively, in the fasting conditions and 113.99%, 110.13% and 111.41%, respectively, in the fed conditions and the 90% confidence intervals were all within the range of 80.00% to 125.00%. It can be concluded from the result that the test product Carbamazepine extended release tablets based on osmotic release system (OROS) are bioequivalent to the reference product Tegretol®-XR tablets.
 Keywords: Bioequivalence, Carbamazepine, Sodium Channel Modulators and Epilepsy