title: Effect of encapsulation on absorption of sumatriptan tablets: data from healthy volunteers and patients during a migraine.
abstract: BACKGROUND
  Some comparative trials of selective serotonin 1B/ID-agonists in migraine have reported -15% lower efficacy for sumatriptan tablets than that reported in placebo-controlled trials.
  
  
  OBJECTIVE
  This study was designed to test the hypothesis that the encapsulation 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-associated gastric stasis.
  
  
  METHODS
  Two randomized, open-label, 2-way crossover trials were conducted to evaluate the absorption and bioequivalence of conventional 50-mg sumatriptan tablets and encapsulated 50-mg sumatriptan tablets in supine, fasted, healthy volunteers (Glaxo Wellcome protocol SUM40270) and supine patients experiencing a migraine (Glaxo Wellcome protocol SUM40268). Absorption was assessed by calculating the area under the plasma concentration-time curve from dosing to 2 hours after dosing (AUC2) and the times to first measurable plasma concentration, 10 ng/mL, 20 ng/mL, and maximum plasma concentration. Data for the AUC from time zero to infinity and maximum plasma concentration were used to assess standard bioequivalence, which is considered to occur when the 90% CIs for the geometric mean treatment ratios (test/reference) 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, 33% men; mean age, 42.7 years). Sumatriptan absorption was delayed with the encapsulated tablet compared with the conventional tablet 0 to 2 hours after dosing, particularly during a migraine. AUC2 values with encapsulated sumatriptan compared with the conventional tablet were 21% lower in healthy volunteers (ratio of capsule/tablet, 0.79; 90% CI, 0.588-1.050) and 27% lower in patients experiencing a migraine (ratio of capsule/tablet, 0.73; 90% CI, 0.519-1.023). Standard bioequivalence was demonstrated in both healthy volunteers and patients experiencing a migraine.
  
  
  CONCLUSIONS
  Encapsulation delayed absorption of sumatriptan 0 to 2 hours after dosing, particularly during a migraine. This delay in absorption of the encapsulated form may account for the lower efficacy of sumatriptan in some comparative studies.
authors: EMF Consulting France, Siret, France.
authors: E
authors: E
authors: Fuseau
authors: O
authors: O
authors: Petricoul
authors: A
authors: A
authors: Sabin
authors: A
authors: A
authors: Pereira
authors: S
authors: S
authors: O'Quinn
authors: S
authors: S
authors: Thein
authors: M
authors: M
authors: Leibowitz
authors: H
authors: H
authors: Purdon
authors: S
authors: S
authors: McNeal
authors: R
authors: R
authors: Salonen
authors: A
authors: A
authors: Metz
authors: P
authors: P
authors: Coates
mesh_terms: D000328:Adult; D018592:Cross-Over Studies; D005260:Female; D006801:Humans; D007408:Intestinal Absorption; D008297:Male; D008875:Middle Aged; D008881:Migraine Disorders / Q000188:drug therapy*; D018170:Sumatriptan / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D013810:Therapeutic Equivalency; D014662:Vasoconstrictor Agents / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use
chemical_list: D014662:Vasoconstrictor Agents; D018170:Sumatriptan