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Pharmacodynamics of acute intranasal administration of verapamil: Comparison with IV and oral administration
Author(s) -
Arnold T. H.,
Tackett R. L.,
Vallner J. J.
Publication year - 1985
Publication title -
biopharmaceutics and drug disposition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.419
H-Index - 58
eISSN - 1099-081X
pISSN - 0142-2782
DOI - 10.1002/bdd.2510060411
Subject(s) - verapamil , nasal administration , bioavailability , oral administration , medicine , crossover study , pharmacology , anesthesia , pharmacokinetics , route of administration , pharmacodynamics , absorption (acoustics) , calcium , physics , alternative medicine , pathology , acoustics , placebo
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.