Nasal absorption of ondansetron in rats: an alternative route of drug delivery.

Purpose: Ondansetron (OND) is a 5-HT3 receptor antagonist that is used therapeutically for the prevention of nausea and vomiting associated with emetogenic cancer therapy. There is a need for nasal drug delivery in specific patient populations where the use of commercially available intravenous and oral dosage forms may be inconvenient and/or unfeasible.

Methods: OND (Zofran Injection, 2 mg/ml) was administered at a dose of 1 mg/kg to male Sprague-Dawley rats intravenously or intranasally (n = 3 in each group). A special surgical procedure was performed to ensure that the drug solution was held in the nasal cavity. OND was injected into the femoral vein for the intravenous group. Blood samples were collected at appropriate times for 60 min. An HPLC method was employed to determine OND in the plasma.

Results: The results clearly showed that OND was readily and rapidly absorbed through the nasal mucosa of the rat. The peak plasma level was attained within 10 min. OND was also completely absorbed as the plasma concentration-time profiles for the two routes were comparable. The terminal elimination half-lives were also similar.

Conclusions: The nasal administration route for OND is apparently as effective as the intravenous route. If one considers the limitations of delivering OND orally or intravenously to patients undergoing emetogenic cancer therapy, it becomes obvious that the intranasal route is a potential alternative modality to prevent nausea and vomiting associated with such therapy.