The pharmacodynamic and pharmacokinetic profile of intranasal crushed buprenorphine and buprenorphine/naloxone tablets in opioid abusers


L. S. Middleton, Departments of Behavioral Science, Center on Drug and Alcohol Research, University of Kentucky, Lexington, KY 40502, USA. E-mail:


Aims  Sublingual buprenorphine and buprenorphine/naloxone are efficacious opioid dependence pharmacotherapies, but there are reports of their diversion and misuse by the intranasal route. The study objectives were to characterize and compare their intranasal pharmacodynamic and pharmacokinetic profiles.

Design  A randomized, double-blind, placebo-controlled, cross-over study.

Setting  An in-patient research unit at the University of Kentucky.

Participants  Healthy adults (n = 10) abusing, but not physically dependent on, intranasal opioids.

Measurements  Six sessions (72 hours apart) tested five intranasal doses [0/0, crushed buprenorphine (2, 8 mg), crushed buprenorphine/naloxone (2/0.5, 8/2 mg)] and one intravenous dose (0.8 mg buprenorphine/0.2 mg naloxone for bioavailability assessment). Plasma samples, physiological, subject- and observer-rated measures were collected before and for up to 72 hours after drug administration.

Findings  Both formulations produced time- and dose-dependent increases on subjective and physiological mu-opioid agonist effects (e.g. ‘liking’, miosis). Subjects reported higher subjective ratings and street values for 8 mg compared to 8/2 mg, but these differences were not statistically significant. No significant formulation differences in peak plasma buprenorphine concentration or time–course were observed. Buprenorphine bioavailability was 38–44% and Tmax was 35–40 minutes after all intranasal doses. Naloxone bioavailability was 24% and 30% following 2/0.5 and 8/2 mg, respectively.

Conclusions  It is difficult to determine if observed differences in abuse potential between intranasal buprenorphine and buprenorphine/naloxone are clinically relevant at the doses tested. Greater bioavailability and faster onset of pharmacodynamic effects compared to sublingual administration suggests a motivation for intranasal misuse in non-dependent opioid abusers. However, significant naloxone absorption from intranasal buprenorphine/naloxone administration may deter the likelihood of intranasal misuse of buprenorphine/naloxone, but not buprenorphine, in opioid-dependent individuals.