Intranasal absorption of sumatriptan and naratriptan: no evidence of local transfer from the nasal cavities to the brain arterial blood in male rats.
Nasal administration to rats of small molecules (tritiated water, tyrosine, and propanol) results in a higher concentration in the brain arterial blood than in other arteries. The preferential distribution is based on a counter current transfer, which takes place between nasal vein blood and brain arterial blood in the cavernous sinus-carotid artery complex. This model was used to investigate whether the antimigraine 5HT(1B/1D) receptor agonists sumatriptan and naratriptan may also be transferred by the system. The ratio of 'head':'heart' plasma concentrations obtained from two carotid catheters after intranasal administration was not different from 1.00 for either compound, and thus, there was no experimental evidence of a preferential local transfer of drug from the nose to the carotid artery circulation. However, plasma concentrations increased from the first minute after intranasal dosing suggesting that sumatriptan and naratriptan are absorbed into the general systemic circulation from the nasal cavity in rats in a first-order fashion with no lag time. This is consistent with the clinical onset of efficacy of sumatriptan after an intranasal dose which occurs as early as 15 min post dose.
Einer-Jensen
N
N
Physiology and Pharmacology, Institute of Medical Biology, University of Southern Denmark, Winsloewparken 21, DK-5000 Odense C, Denmark.
Larsen
L
L
Deprez
S
S
Starns
E
E
Schwartz
S
S
D000042:Absorption; D000818:Animals; D002536:Cerebral Arteries / Q000378:metabolism*; D007211:Indoles / Q000008:administration & dosage / Q000493:pharmacokinetics*; D008297:Male; D009296:Nasal Cavity / Q000378:metabolism*; D010880:Piperidines / Q000008:administration & dosage / Q000493:pharmacokinetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017366:Serotonin Receptor Agonists / Q000493:pharmacokinetics*; D018170:Sumatriptan / Q000008:administration & dosage / Q000493:pharmacokinetics*; D014363:Tryptamines
D007211:Indoles; D010880:Piperidines; D017366:Serotonin Receptor Agonists; D014363:Tryptamines; D018170:Sumatriptan; C106783:naratriptan