Pharmacokinetics and bioequivalence evaluation of two oral formulations of topiramate tablets in healthy Chinese male volunteers under fasting and fed conditions

Topiramate is an antiepileptic drug (AED) that is effective in treating various types of epilepsy. This study evaluated the bioequivalence and safety of two topiramate tablets in healthy Chinese subjects under fasting and fed conditions. We designed an open-label, randomized, single-dose, two-period, crossover trial protocol. Two independent trials were conducted, each including 26 volunteers. In the fed trial, subjects were randomly assigned to two groups (1:1 ratio) to receive either 100 mg of test formulation or reference formulation of topiramate. After a 21-day washout period, crossover administration was implemented. The fasting trial design was similar to that of the fed trial. Plasma concentrations of topiramate were determined using a validated method (high-performance liquid chromatography-tandem mass spectrometry, HPLC-MS/MS). Pharmacokinetic (PK) parameters such as maximum plasma drug concentration (C_max), time to reach maximum concentration (T_max), and the area under the plasma concentration-time curve from time 0 to 72 h (AUC_0-72) were calculated using a non-compartment model to evaluate the bioequivalence of two formulations. The safety of volunteers was monitored during the entire study. In the fasting trial, 90% confidence intervals (CIs) of geometric mean ratios (GMRs) of the test to reference formulations were 101.26-112.94% for C_max and 98.50-102.69% for AUC_0-72, all within the recognized bioequivalence range of 80.00-125.00%. In the fed trial, 90% CIs of GMRs of the test to reference formulations were 92.08-101.54% for C_max and 95.81-99.79% for AUC_0-72, both were within the bioequivalence range of 80.00-125.00%. Research findings indicated that the two topiramate formulations were bioequivalent and had a favorable safety profile.