Topiramate: An in Vitro and in Vivo Comparison between the Pharmacokinetic Properties of a Generic (Sincronil) and the Reference (Topamax) Formulation

摘要

The use of generic formulation of therapeutic agents may allow a significant reduction of costs for patients and the National Health Services. This is particularly true for drugs used in prolonged therapies such as topiramate which is effective in the treatment of epilepsy, migraine, alcohol abuse and psychiatric conditions. The purposes of this study were: 1) evaluate Topiramate (50 mg) release in vitro from a generic (Sincronil) and the reference formulation (Topamax); 2) compare the above mentioned generic and reference formulations in bioavailability studies in healthy volunteers. Dissolution tests in vitro showed that more than 95% of the active principle was released within 15 minutes both from the reference and the generic formulation. No difference in release kinetics was found between the two topiramate preparations. In vivo pharmacokinetic data were obtained by administering 1 tablet containing 50 mg of topiramate of each of the two formulations to 28 healthy volunteers under fasting conditions, using a randomized, single-dose, open-label, 2-way crossover design. The treatment phases were separated by a washout period of 21 days. The maximum concentration reached in plasma (Cmax) for the reference and the generic formulation, were 946 ± 308 and 849 ± 247 (ng/mL) and the area under the curve (AUC0-t) were 35,900 ± 7800 and 34,300 ± 8100 (ng·h/mL) respectively. The data indicate that the rate and extent of absorption of the reference or generic 50 mg topiramate formulation are not significantly different and suggest that the therapeutic effects of the two preparations do not significantly differ.