">Table 2. Pharmacokinetic parameters of Sincronil and Topamax.

Table 3. Bioequivalence of Topamax and Sincronil as evaluated with the ratio of the least squares means and the 90% geometric confidence interval (CI) of the AUC0-inf AUC0-t and Cmax.

cokinetic data for preparations containing 50 mg topira mate are reported, since in previous studies in healthy subjects, the dose of topiramate studied were 100 - 200 mg, possibly because the doses of the drug used for the treatment of epilepsy are larger than those used in migraine prevention [11-14]. Considering published data on topiramate pharmacokinetic after the administration of 100 - 200 mg, our results extend previous observation on a linear decrease/increases in plasma Cmax proportional to the dose administered. As previously reported, topiramate half-life was relatively long (see Table 2) and for this reason the wash out period for the present study was set at 21 days, a period long enough to allow the clearance of the drug after each dosing. Finally, it is important to mention that topiramate absorption should not change after food intake, thus the data obtained in the fasting condition reasonably apply to the fed condition.

Topiramate efficacy in epilepsy and migraine is included in several treatment guidelines [5,15-17] and excellent clinical results have been obtained for other pathological conditions such as alcoholism [5]. The overall risk/benefit ratio of its standard use is considered favorable and a recent report dealing with migraine prevention, states that topiramate inclusion in the drug armamentarium used in these patients is one of the outstanding advances of the last ten years in this field [10].

REFERENCES

  1. C. A. Jackevicius, M. M. Chou, J. S. Ross, N. D. Shah, and H. M. Krumholz, “Generic Atorvastatin and Health Care Costs,” New England Journal of Medicine, Vol. 366, No. 3, 2011, pp. 201-204. doi:10.1056/NEJMp1113112
  2. C. Chu, E. Rudant, M. Bonvalet, H. Agostini, P. Cavalie, L. Bonhomme-Faivre, J. Frenkiel, J. Taillandier, A. Boissonnas, D. Vittecoq and B. Wyplosz, “Generic Drug Prescriptions Following Hospital Discharge: A Prospective Study in France,” European Journal of Internal Medicine, Vol. 22, No. 5, 2011, pp. e45-e49. doi:10.1016/j.ejim.2011.01.016
  3. M. Yamada and T. E. Welty, “Generic Substitution of Antiepileptic Drugs: A Systematic Review of Prospective and Retrospective Studies,” The Annals of Pharmacotherapy, Vol. 45, No. 11, 2011, pp. 1406-1415. doi:10.1345/aph.1Q349
  4. R. P. Shank and B. E. Maryanoff, “Molecular Pharmacodynamics, Clinical Therapeutics, and Pharmacokinetics of Topiramate,” CNS Neuroscience & Therapeutics, Vol. 14, No. 2, 2008, pp. 120-142. doi:10.1111/j.1527-3458.2008.00041.x
  5. B. A. Johnson, N. Rosenthal, J. A. Capece, F. Wiegand, L. Mao, K. Beyers, A. McKay, N. Ait-Daoud, R. F. Anton, D. A. Ciraulo, H. R. Kranzler, K. Mann, S. S. O’Malley, and R. M. Swift, “Topiramate for Treating Alcohol Dependence: A Randomized Controlled Trial,” JAMA, Vol. 298, 2007, pp. 1641-1651. doi:10.1001/jama.298.14.1641
  6. P. Crawford, M. Feely, A. Guberman and G. Kramer, “Are There Potential Problems with Generic Substitution of Antiepileptic Drugs? A Review of Issues,” Seizure, Vol. 15, No. 3, 2006, pp. 165-176. doi:10.1016/j.seizure.2005.12.010
  7. J. E. Desmarais, L. Beauclair and H. C. Margolese, “Switching from Brand-Name to Generic Psychotropic Medications: A Literature Review,” CNS Neuroscience & Therapeutics, Vol. 17, No. 6, 2011, pp.750-760. doi:10.1111/j.1755-5949.2010.00210.x
  8. A. S. Kesselheim, M. R. Stedman, E. J. Bubrick, J. J. Gagne, A. S. Misono, J. L. Lee, M. A. Brookhart, J. Avorn and W. H. Shrank, “Seizure Outcomes Following the Use of Generic versus Brand-Name Antiepileptic Drugs: A Systematic Review and Meta-Analysis,” Drugs, Vol. 70, No. 6, 2010, pp. 605-621. doi:10.2165/10898530-000000000-00000
  9. M. Maliepaard, N. Banishki, C. C. Gispen-de Wied, S. Teerenstra and A. J. Elferink, “Interchangeability of Generic Anti-Epileptic Drugs: A Quantitative Analysis of Topiramate and Gabapentin,” European Journal of Clinical Pharmacology, Vol. 67, No. 10, 2011, pp. 1007- 1016. doi:10.1007/s00228-011-1041-4
  10. L. Edvinsson and M. Linde, “New Drugs in Migraine Treatment and Prophylaxis: Telcagepant and Topiramate,” Lancet, Vol. 376, No. 9741, 2010, pp. 645-655. doi:10.1016/S0140-6736(10)60323-6
  11. W. E. Rosenfeld, “Topiramate: A Review of Preclinical, Pharmacokinetic, and Clinical Data,” Clinical Therapeutics, Vol. 19, No. 6, 1997, pp. 1294-1308. doi:10.1016/S0149-2918(97)80006-9
  12. J. H. Park, Y. S. Park, M. H. Lee, S. Y. Rhim, J. C. Song, S. J. Lee, J. M. Kim, L. M. Shaw, and J. S. Kang, “Determination of Plasma Topiramate Concentration Using LC-MS/MS for Pharmacokinetic and Bioequivalence Studies in Healthy Korean Volunteers,” Biomedical Chromatography, Vol. 22, No. 8, 2008, pp. 822-829. doi:10.1002/bmc.995
  13. A. Pineyro-Lopez, E. Pineyro-Garza, M. Gomez-Silva, R. Reyes-Araiza, M. A. Flores-Diego, S. Borrego-Alvarado, M. E. Gamino-Pena, R. Vargas-Zapata and M. E. Salazar-Leal, “Bioequivalence of Single 100-mg Doses of Two Oral Formulations of Topiramate: An Open-Label, Randomized-Sequence, Two-Period Crossover Study in Healthy Adult Male Mexican Volunteers,” Clinical Therapeutics, Vol. 31, 2009, pp. 411-417. doi:10.1016/j.clinthera.2009.02.001
  14. I. Saavedra, E. Tamayo, A. Gamboa, J. Sasso, N. Varela, I. Moreno, D. Marchant, D. Caceres and L. Quinones, “Relative Bioavailability Study with Two Oral Formulations of Topiramate Using a Validated UPLC-MS/MS Method,” International Journal of Clinical Pharmacology, Therapy, & Toxicology, Vol. 48, 2010, pp. 342-348.
  15. E. Beghi, “Efficacy and Tolerability of the New Antiepileptic Drugs: Comparison of Two Recent Guidelines,” Lancet Neurology, Vol. 3, No. 10, 2004, pp. 618-621. doi:10.1016/S1474-4422(04)00882-8
  16. A. May, M. Leone, J. Afra, M. Linde, P. S. Sandor, S. Evers and P. J. Goadsby, “EFNS Guidelines on the Treatment of Cluster Headache and Other TrigeminalAutonomic Cephalalgias,” European Journal of Neurology, Vol. 13, 2006, pp. 1066-1077. doi:10.1111/j.1468-1331.2006.01566.x
  17. S. Evers, J. Afra, A. Frese, P. J. Goadsby, M. Linde, A. May and P. S. Sandor, “EFNS Guideline on the Drug Treatment of Migraine—Revised Report of an EFNS Task Force,” European Journal of Neurology, Vol. 16, 2009, pp. 968-981.doi:10.1111/j.1468-1331.2009.02748.x

Journal Menu >>