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GEORGE A. DAVIS, PHARM.D., is Medical Scientific Manager, Sanofi Aventis, Lexington, KY; at the time of this study he was Assistant Professor, College of Pharmacy, University of Kentucky (UK), Lexington. ANITA C. RUDY, PH.D., is Pharmaceutical Scientist, Intranasal Technology, Inc., Lexington. SANFORD M. ARCHER, M.D., and DANIEL P. WERMELING, PHARM.D., are Associate Professors, College of Pharmacy, UK.

Address correspondence to Dr. Rudy at Intranasal Technology, Inc., UK Coldstream Research Campus, 1513 Bull Lea Boulevard, Lexington, KY 40511-1200 (arudy{at}intranasal.com).

Purpose. 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. Conclusion. Single-dose intranasal butorphanol was rapidly absorbed and had high absolute bioavailability in healthy volunteers. Index terms: Absorption; Analgesics and antipyretics; Blood levels; Butorphanol tartrate; Dosage; Drug administration routes; Drugs, availability; Excretion; Nasal preparations; Pharmacokinetics; Rate constants; Toxicity