title: Comparison of intranasal versus intravenous verapamil bioavailability.
abstract: Intranasal verapamil administration may limit intrasubject variability encountered due to the metabolism differences of the d and l-isomers. We simultaneously measured verapamil/norverapamil concentrations, PR interval, heart rate (HR), and mean arterial pressure (MAP) in six healthy volunteers receiving verapamil 5 mg intranasally and intravenously on two separate occasions. Two subjects achieved measurable verapamil concentrations after intranasal administration with a mean bioavailability of 16.1%. Intranasal bioavailability was limited secondary to instillation volume. No relationship between HR, MAP and verapamil concentration was noted. A relationship between mean intravenous verapamil concentration and mean PR interval was observed; however, extensive interpatient variability existed: two subjects demonstrated enough counterclockwise hysteresis to skew mean data. Mean data may falsely represent the verapamil concentration-effect relationship. Intranasal verapamil administration is limited by instillation volume. Development of a concentrated dosage form is necessary to assess bioavailability. Concentration-effect relationships are more accurately described using individual, rather than mean data.
authors.affiliation: Department of Medicine, Moses H. Cone Memorial Hospital, Greensboro, NC.
authors.forename: S
authors.initials: S
authors.lastname: Watling
authors.forename: J
authors.initials: J
authors.lastname: Engelhardt
authors.forename: R
authors.initials: R
authors.lastname: Kandrotas
authors.forename: P
authors.initials: P
authors.lastname: Gal
authors.forename: P
authors.initials: P
authors.lastname: Kroboth
authors.forename: H
authors.initials: H
authors.lastname: Smith
authors.forename: M
authors.initials: M
authors.lastname: Johnson
mesh_terms: D000281:Administration, Intranasal; D000328:Adult; D001682:Biological Availability; D001794:Blood Pressure / Q000187:drug effects; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D014700:Verapamil / Q000008:administration & dosage / Q000493:pharmacokinetics*
chemical_list: D014700:Verapamil