Relative bioavailability study with two oral formulations of topiramate using a validated UPLC-MS/MS method

Abstract

Changes in bioavailability of anticonvulsant drugs such as topiramate may cause loss of or worsened seizure control. Thus, the purpose of this study was to evaluate, in a double-blind crossover design, the bioavailability between two oral formulations of topiramate in healthy volunteers after a single dose. The protocol, approved by the Institutional Committee of Ethics, consisted of administration of 1 tablet of 100 mg of topiramate of each formulation (Toprel™ and Topamax™), to 20 healthy volunteers after a 12 h overnight fast, using an open, two-period, randomized, crossover and double-blind design. Thus, the plasma concentrations (Cp) of topiramate weremeasured at predetermined intervals of time, from 0 to 24 h, using a validated UPLC-MS/MS method. Based on plasma concentration-time profiles we obtained the following pharmacokinetic parameters: AUC0– 63,418.31 ± 22,141.69 and 67,094.70 ± 22,487.2 ngh/ml; AUC0–24: 30,421.02 ± 9,964.0 and 30,489.35 ± 9,407.17, ng h/ml; tmax: 2.77 ± 1.76 and 1.95 ± 1.89 h; Cmax: 2,143.33 ± 724.26 and 2,262.51 ± 751.12 ng/ml, for A (Toprel™) and B (Topamax ™), respectively. All these differences were not statically significant with 90% confidence interval. The test of bioequivalence showed that Cmax, AUC0–24 and AUC0– parameters are found within the range of 0.8 – 1.25 recommended by the FDA with a probability of bioequivalence of 100%. In accordance with these results, we can conclude that Toprel™ 100 mg, A (Test), is a bioequivalent generic and interchangeable with Topamax ™ 100 mg, B (Reference).