Uptake and biodistribution of rizatriptan to blood and brain following different routes of administration in rats

The objective of the present study was to investigate the biodistribution profiles of rizatriptan in the blood and brain of Wistar rats after peroral, subcutaneous, intranasal and intratracheal administration with a particular view to determining the applicability of inhalation delivery to achieve rapid and high availability of the drug in both blood and the brain. Following the intratracheal administration of the drug (4.0 mg/kg) to the rats, the absolute bioavailability was found to be 91.2%, significantly higher than those from intranasal or peroral routes, and Tmax in plasma and brain was attained within 2 min, significantly shorter than the Tmax of intranasal (∼10 min in both plasma and brain), subcutaneous (16.7 min in plasma and 22.5 min in brain) and peroral (30.0 min in plasma and 45.0 min in brain) administration. In addition, other pharmacokinetic parameters associated with rapid onset of action including AUCplasma/brain and Cmax, of intratracheal instillated rizatriptan appeared also to be comparable or superior to those of other delivered routes. Although AUCbrain/AUCplasma ratios after intranasal delivery (43.4%) differed significantly from the ratios shown after intratracheal instillation (23.2%), the AUCbrain 0–120 min via the latter routes was slightly but not significantly higher than that from the former routes. The results in the present study indicated that pulmonary delivery of rizatriptan may achieve maximum plasma and brain concentrations significantly more rapidly compared with intranasal, subcutaneous and peroral administration and be a promising delivery method with extremely rapid onset of action in the pain relief of migraine.