Distribution of intranasal C-zolmitriptan assessed by positron emission tomography.
Nine healthy volunteers aged 18-28 years were recruited into this open, single-centre, two-phase trial. In phase 1, two volunteers received a single dose of 11C-zolmitriptan 2.5 mg administered as a nasal spray and then underwent positron emission tomography (PET) scanning to determine the most appropriate times for scanning in phase 2. In phase 2, six volunteers received two doses and an additional volunteer one dose of 11C-zolmitriptan 2.5 mg intranasally. Volunteers underwent PET scanning over sectors covering one of the nasopharynx, lungs or abdomen, for up to 1.5 h postdose. The brain was also scanned and plasma zolmitriptan levels were measured. Almost 100% of the administered dose was detected in the nasopharynx immediately after dosing. This declined thereafter to about 50% at 20 min and to 35% at 80 min after dosing. Radioactivity appeared slowly in the upper abdomen, with 25% of given radioactivity detected at 20 min and persisting until 80 min after dosing. Minimal radioactivity was detected in the lungs. Radioactivity was detectable within brain tissue suggesting central penetration of zolmitriptan. Zolmitriptan in plasma had approached its maximum concentration by 15 min postdose. The data indicate initial absorption across the nasal mucosa contributing to an early systemic availability. 11C-Zolmitriptan administered intranasally was well tolerated.
Yates
R
R
AstraZeneca, Macclesfield, UK, and Uppsala University PET Centre, Sweden.
Sörensen
J
J
Bergström
M
M
Antoni
G
G
Nairn
K
K
Kemp
J
J
Långström
B
B
Dane
A
A
D000280:Administration, Inhalation; D000293:Adolescent; D000328:Adult; D001921:Brain; D002250:Carbon Radioisotopes / Q000493:pharmacokinetics; D005260:Female; D006801:Humans; D008297:Male; D008657:Metabolic Clearance Rate; D009297:Nasal Mucosa / Q000378:metabolism*; D009305:Nasopharynx / Q000000981:diagnostic imaging / Q000378:metabolism*; D009666:Nose / Q000000981:diagnostic imaging; D009928:Organ Specificity; D023303:Oxazolidinones / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D049268:Positron-Emission Tomography / Q000379:methods*; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D020545:Respiratory Mucosa / Q000000981:diagnostic imaging / Q000378:metabolism*; D017366:Serotonin Receptor Agonists / Q000008:administration & dosage / Q000493:pharmacokinetics; D014018:Tissue Distribution; D014363:Tryptamines / Q000008:administration & dosage* / Q000493:pharmacokinetics*
D002250:Carbon Radioisotopes; D023303:Oxazolidinones; D019275:Radiopharmaceuticals; D017366:Serotonin Receptor Agonists; D014363:Tryptamines; C089750:zolmitriptan