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

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 were measured 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: AUC(0-inf) 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 x h/ml; tmax: 2.77 +/- 1.76 and 1.95 +/- 1.89 h; C(max): 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, AUC(0-24) and AUC(0-inf) 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).