Bioequivalence of carbamazepine chewable and conventional tablets: single-dose and steady-state studies.

Single-dose and steady-state studies were carried out on separate occasions to examine the bioequivalence of the newly formulated carbamazepine chewable tablet. In the single-dose study, the plasma levels resulting from 2 X 200-mg conventional tablets (CT), 4 X 100-mg chewable tablets swallowed whole (SW), and 4 X 100-mg chewable tablets chewed before swallowing (CHEW) were compared. A randomized 3 X 3 Latin-square design balanced for residual effects, with a 3-week washout period, was used (n = 6). Plasma samples were analyzed by a specific GC method for carbamazepine. The following parameters were used for evaluation: AUC, Cmax, tmax, and t1/2. None of the parameters were significantly different except Cmax and t1/2 values for CHEW and CT. The Cmax was 25% higher and t1/2 was 11% shorter for CHEW than CT. The impact of differences in the peak plasma levels at steady state were examined by pharmacokinetic projection (400 mg b.i.d.) based on the single-dose data and with simulated induction equal to a 50% reduction in t1/2. The projected steady-state CT and CHEW plasma concentrations were similar, with a difference of only 4%. The results demonstrate the bioequivalence of the dosage forms with respect to the extent of absorption, and similar steady-state concentrations of carbamazepine in plasma can be expected. To test the conclusion from the projected study, a separate bioequivalence study to compare CHEW relative to CT was performed at steady state in normal volunteers (200 mg b.i.d.).(ABSTRACT TRUNCATED AT 250 WORDS)

RCT Entities:   Population Interventions Outcomes