Comparison of intranasal versus intravenous verapamil bioavailability.
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.
Watling
S
S
Department of Medicine, Moses H. Cone Memorial Hospital, Greensboro, NC.
Engelhardt
J
J
Kandrotas
R
R
Gal
P
P
Kroboth
P
P
Smith
H
H
Johnson
M
M
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*
D014700:Verapamil