title: Rapid absorption of sumatriptan powder and effects on glyceryl trinitrate model of headache following intranasal delivery using a novel bi-directional device.
abstract: OBJECTIVE
  The aim was to investigate the pharmacokinetics of intranasal sumatriptan (administered using a novel bi-directional powder delivery device) and study its effects on quantitative electroencephalography in patients with migraine. The safety profiles of the two formulations were also compared.
  
  
  METHODS
  The pharmacokinetics of intranasal sumatriptan (10 mg and 20 mg) administered using a novel breath-actuated bi-directional powder delivery device were compared with subcutaneous sumatriptan (6 mg), along with an investigation of their effects on the electroencephalogram (EEG) following glyceryl trinitrate (GTN) challenge in 12 patients with migraine using a randomized, three-way cross-over design.
  
  
  RESULTS
  Following intranasal delivery, median t(max) was 20 min with both doses compared with 10 min after the subcutaneous dose. Mean +/- SD values for C(max) were 96 +/- 25, 11 +/- 7 and 16 +/- 6 ng/ml for subcutaneous, intranasal 10 mg and intranasal 20 mg formulations, respectively. Values for area under the curve were also lower with the intranasal doses. Intranasal and subcutaneous sumatriptan induced similar EEG changes characterized by reduced theta-power and increased beta-power. The majority of study participants were free of pain according to the headache severity score with all treatments from 15 min through to 8 h post-dose. All treatments were well tolerated and there were no reports of bitter aftertaste after intranasal delivery. Sumatriptan was rapidly absorbed after intranasal administration using the new device. Using the GTN challenge, sumatriptan powder delivered intranasally at a dose of 20 mg by the new device had effects similar to those of subcutaneous sumatriptan on EEG and reported headache pain, despite much lower systemic exposure.
  
  
  CONCLUSIONS
  Administration of sumatriptan intranasally at doses of 10 mg and 20 mg by the breath actuated bi-directional powder delivery device results in rapid absorption. Delivery to target sites beyond the nasal valve induced a similar EEG profile to subcutaneous sumatriptan 6 mg and prevented migraine attacks in patients following GTN challenge. Intranasal administration of sumatriptan powder with the breath actuated bi-directional powder delivery device was well tolerated.
authors.affiliation: Forenap FRP, 27 rue du 4ème RSM, B.P. 27, 68250 Rouffach, France. remy.luthringer@forenap.com
authors.forename: Remy
authors.initials: R
authors.lastname: Luthringer
authors.forename: Per G
authors.initials: PG
authors.lastname: Djupesland
authors.forename: Colin D
authors.initials: CD
authors.lastname: Sheldrake
authors.forename: Anthony
authors.initials: A
authors.lastname: Flint
authors.forename: Peter
authors.initials: P
authors.lastname: Boeijinga
authors.forename: Philippe
authors.initials: P
authors.lastname: Danjou
authors.forename: Agnès
authors.initials: A
authors.lastname: Demazières
authors.forename: Graeme
authors.initials: G
authors.lastname: Hewson
mesh_terms: D000042:Absorption; D000281:Administration, Intranasal; D000328:Adult; D016503:Drug Delivery Systems / Q000295:instrumentation*; D004569:Electroencephalography / Q000187:drug effects*; D005260:Female; D006801:Humans; D007279:Injections, Subcutaneous; D008297:Male; D008881:Migraine Disorders / Q000188:drug therapy*; D005996:Nitroglycerin; D011208:Powders / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology; D018170:Sumatriptan / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology
chemical_list: D011208:Powders; D017366:Serotonin Receptor Agonists; D018170:Sumatriptan; D005996:Nitroglycerin