Effect of encapsulation on absorption of sumatriptan tablets: Data from healthy volunteers and patients during a migraine

Background: Some comparative trials of selective serotonin 1B/1D-agonists i n migraine have reported similar to 15% lower efficacy for sumatriptan tabl ets than that reported in placebo-controlled trials. Objective: This study was designed to test the hypothesis that the encapsul ation methods used to mask active drug may delay absorption of sumatriptan from dosing to 2 hours after dosing (the traditional end point in clinical trials of migraine treatment), an effect that may be enhanced by migraine-a ssociated gastric stasis. Methods: Two randomized, open-label, 2-way crossover trials were conducted to evaluate the absorption and bioequivalence of conventional 50-mg sumatri ptan tablets and encapsulated 50-mg sumatriptan tablets in supine, fasted, healthy volunteers (Glaxo Wellcome protocol SUM40270) and supine patients e xperiencing a migraine (Glaxo Wellcome protocol SUM40268). Absorption was a ssessed by calculating the area under the plasma concentration-time curve f rom dosing to 2 hours after dosing (AUC(2)) and the times to first measurab le plasma concentration, 10 ng/mL, 20 ng/mL, and maximum plasma concentrati on. Data for the AUC from time zero to infinity and maximum plasma concentr ation were used to assess standard bioequivalence, which is considered to o ccur when the 90% CIs for the geometric mean treatment ratios (test/referen ce) fall between 0.8 and 1.25. Results: Study 1 included 26 healthy subjects (73% men, 27% women; mean age , 39.1 years), and study 2 included 30 patients with migraine (67% women, 3 3% men; mean age, 42.7 years). Sumatriptan absorption was delayed with the encapsulated tablet compared with the conventional tablet 0 to 2 hours afte r dosing, particularly during a migraine. AUG, values with encapsulated sum atriptan compared with the conventional tablet were 21% lower in healthy vo lunteers (ratio of capsule/ tablet, 0.79, 90% CI, 0.588-1.050) and 27% lowe r in patients experiencing a migraine (ratio of capsule/tablet, 0.73; 90% C I, 0.519-1.023). Standard bioequivalence was demonstrated in both healthy v olunteers and patients experiencing a migraine. Conclusions: Encapsulation delayed absorption of sumatriptan 0 to 2 hours a fter dosing, particularly during a migraine. This delay in absorption of th e encapsulated form may account for the lower efficacy of sumatriptan in so me comparative studies.