Bioavailability of intranasal butorphanol administered from a single-dose sprayer.
OBJECTIVE
The bioavailability and tolerability of single doses of intranasal butorphanol tartrate using a single-dose, metered sprayer were studied.


METHODS
In this open-label, randomized, three-way crossover study, 24 healthy volunteers received three treatments: (1) 2 mg of i.v. butorphanol (treatment A), (2) 2 mg of intranasal butorphanol (treatment B), and (3) 1 mg of intranasal butorphanol (treatment C). The three treatments received by each subject were separated by six-day washout periods. Venous blood samples (10 mL each) were obtained from an indwelling catheter at 0 (predose), 5, 10, 15,20,30, and 45 minutes and 1,2,3,4,6,8, 12, and 16 hours after butorphanol administration. Pharmacokinetic parameters were determined using standard noncompartmental methods with log-linear least-squares regression analysis to determine the elimination-rate constants.


RESULTS
Intranasal butorphanol 1 and 2 mg administered using unit dose sprayers had a mean bioavailability of approximately 80%, which is higher than the percentage reported with the commercially available multidose product (61-69%). The absorption of intranasal butorphanol was rapid, with a median time to reach maximum concentration of 20 minutes (range, 10-60 minutes). Elimination profiles were comparable among all treatments. There were no clinically significant changes in the results of physical examinations, nasal evaluations, or laboratory tests related to butorphanol treatment. Most adverse effects reported were mild to moderate and as expected for this drug.


CONCLUSIONS
Single-dose intranasal butorphanol was rapidly absorbed and had high absolute bioavailability in healthy volunteers.
Davis
George A
GA
Sanofi Aventis, Lexington, KY, USA.
Rudy
Ani Ia C
AIa
Archer
Sanford M
SM
Wermeling
Daniel P
DP
D000281:Administration, Intranasal; D000328:Adult; D019540:Area Under Curve; D001682:Biological Availability; D002077:Butorphanol / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics; D018592:Cross-Over Studies; D004334:Drug Administration Schedule; D005260:Female; D006207:Half-Life; D006801:Humans; D007275:Injections, Intravenous; D007297:Inpatients; D008297:Male; D009330:Nebulizers and Vaporizers; D013678:Technology, Pharmaceutical / Q000295:instrumentation / Q000379:methods
D002077:Butorphanol