Pharmacokinetics of butorphanol tartrate administered from single-dose intranasal sprayer.
OBJECTIVE
The pharmacokinetics and tolerability of single and multiple doses of intranasal butorphanol tartrate using a single-dose metered sprayer were studied.


METHODS
In this randomized, open-label, two-way crossover study, 24 healthy subjects received either 1 or 2 mg of intranasal butorphanol as a single dose (treatment A) and 1 or 2 mg of intranasal butorphanol every six hours for seven doses (treatment B). During phase 1, 12 subjects selected at random received a single 1-mg dose and the other 12 a single 2-mg dose. During phase 2, those who received the 1-mg single dose received 1 mg every six hours for seven doses. During phase 3, those who received the 2-mg single dose received 2 mg every six hours for seven doses. Serial blood samples were collected over 12 hours. Pharmacokinetic parameters were determined using noncompartmental methods.


RESULTS
Mean (coefficient of variation) values for the area under the concentration-versus-time curve (AUC) from time zero to infinity (AUC0-infinity) were 4.15 (26.4%) and 10.42 (19.6%) ng.hr/ml after single doses of 1 and 2 mg of butorphanol, respectively. At steadly state, mean values for the AUC from time zero to the dosing interval (AUC0-tau) were 4.82 (40.2%) and 10.60 (22.3%) ng.hr/mL, respectively. The accumulation indices were around 2 for both the 1- and 2-mg doses. Median time to maximum concentration values ranged from 15 to 30 minutes for each treatment. Dose-normalized parameters AUC0-infinity. AUC0-tau and maximum concentration (Cmax) were significantly larger after a single 2-mg versus 1-mg dose (p < 0.05).


CONCLUSIONS
Intranasal butorphanol has rapid absorption and predictable accumulation after multiple doses administered with single-dose metered sprayers. Intranasal administration of butorphanol was well tolerated and adverse events were generally mild to moderate in severity and as expected for this drug.
Division of Pharmacy Practice and Science, College of Pharmacy, University of Kentucky, A.B. Chandler Medical Center, 800 Rose Street, Room C117, Lexington, KY 40536-0293, USA. gadavi00@email.uky.edu
George A
GA
Davis
Anita C
AC
Rudy
Sanford M
SM
Archer
Daniel P
DP
Wermeling
D000281:Administration, Intranasal; D000293:Adolescent; D000328:Adult; D000701:Analgesics, Opioid / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D002077:Butorphanol / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D018592:Cross-Over Studies; D004334:Drug Administration Schedule; D004864:Equipment and Supplies; D005260:Female; D006801:Humans; D008297:Male; D019999:Pharmaceutical Solutions; D013997:Time Factors
D000701:Analgesics, Opioid; D019999:Pharmaceutical Solutions; D002077:Butorphanol