Pharmacodynamics of acute intranasal administration of verapamil: comparison with i.v. and oral administration.

The present study was conducted in order to examine the intranasal administration of verapamil and compare this route to oral and intravenous administration in a 3 way crossover protocol in five dogs. Unanesthetized, adult mongrel dogs were given verapamil intravenously (0.5 mg/kg), orally (2.5 mg/kg) and intranasally (0.75 mg/kg) with at least a 3-4 day washout period between each administration. Blood samples were collected over a 10 hour period and analyzed for verapamil using HPLC with fluorescence detection. A lead II ECG was monitored to determine the effects of verapamil on heart rate and P-R interval. Following intravenous administration, verapamil was distributed according to a two compartment model. Bioavailability (corrected for dose and elimination rate constant) following intranasal administration (36% +/- 7%) was approximately 3 fold that after oral administration (13% +/- 3%). Absorption from the nasal cavity appeared instantaneous compared to an absorption half-life of 50 +/- 6 min after oral administration. All three routes of administration resulted in significant increases in heart rate and increases in the P-R interval. Maximal P-R interval prolongation occurred after peak plasma concentrations of verapamil. The results of this study suggest that the intranasal route is a viable alternative route of administration for verapamil.