Bioequivalence Study of 2 Orodispersible Formulations of Zolmitriptan 5 mg in Healthy Volunteers

Abstract

A bioequivalence study of 2 zolmitriptan (CAS 139264-17-8) orodispersible tablet formulations was carried out in 26 healthy volunteers according to an open label, randomized, 2-period, 2-sequence, crossover, single dose and fasting conditions design. The test and reference formulations were administered in 2 treatment days, separated by a washout period of 7 days. Plasma concentrations of zolmitriptan and its active metabolite (N-desmethyl-zolmitriptan) were obtained by LC/MS/MS method. Log-transformed AUCs and C_max values were tested for bioequivalence based on the ratios of the geometric means (test/reference). T_max was analysed nonparametrically. The 90% confidence intervals of the geometric mean values for the test/reference ratios for AUC_0-t and C_max were within the bioequivalence acceptance range of 80–125%. According to the European Guideline [1] it may be therefore concluded that test formulation of zolmitriptan 5 mg orodispersible tablet is bioequivalent to the reference formulation.

Key words

antimigraine agent - bioequivalence - CAS 139264-17-8 - zolmitriptan - pharmacokinetics

*

^* working at the institution at the time of the trial

• References

• 1 Guideline on the Investigation of Bioequivalence (CPMP/EWP/QWP/1401/98 Rev. 1/Corr, London 20 January 2010)
• 2 Goadsby P, Lipton R, Ferrari M. Migraine. Current understanding and treatment. N Engl J Med 2002; 346: 257-270
• 3 Peterlin BL, Papoport AM. Clinical pharmacology of the serotonin receptor agonist, zolmitriptan. Expert Opin Drug Metab Toxicol 2007; 3: 899-911
• 4 electronic Medicines Compendium (eMC) [Internet] Summary of Products Characteristics of Zomig Rapimelt 5 mg orodispersible tablets. Available from: http://www.medicines.org.uk/emc/medicine/15386 Accessed on 2012/04/17
• 5 Seaber E, On N, Phillips S et al. The tolerability and pharmacokinetics of the novel antimigraine compound 311C90 in healthy male volunteers. Br J Clin Pharmacol 1996; 41: 141-147
• 6 Spencer CM, Gunasekara NS, Hills C. Zolmitriptan. A review of its use in migraine. Drugs 1999; 58: 347-374
• 7 CPMP/ICH/135/95, ICH Topic E6 (R1): Guideline for Good Clinical Practice, July 2002
• 8 WinNonLin™ Professional Edition software v5.2 (Pharsight Corporation, Mountain View, CA). http://pharsight.com
• 9 Zhang P. A simple formula for sample size calculation in equivalence studies. J Biopharm Stat 2003; 13 (03) 529-538
• 10 Schuirmann DJ. A comparison of the two one-sided tests procedure and the power approach for assessing the equivalence of average bioavailability. J Pharmacokinet Biopharm 1987; 15: 657-680
• 11 Hauschke D, Steinijans VW, Diletti E. A distribution-free procedure for the statistical analysis of bioequivalence studies. Int J Clin Pharmacol Ther Toxicol 1990; 28: 72-78