Low-Dose Naloxone Provides an Abuse-Deterrent Effect to Buprenorphine

In developmental research, plasma buprenorphine concentrations comparable to a 2 mg buprenorphine–naloxone (BN) sublingual tablet have been achieved with a 0.75 mg dose of BN buccal film, a small, bioerodible polymer film for application to mucosal membranes. 

This was a randomized, double-blind, placebo-controlled, single-dose, four-period crossover study in opioid-dependent subjects with chronic pain receiving >100 mg oral morphine equivalents daily who experienced withdrawal following a naloxone challenge dose. 

The objective of the study was to determine if intravenous (IV) naloxone doses of 0.1 and 0.2 mg would produce a withdrawal response when coadministered with a 0.75 mg IV dose of buprenorphine. Fifteen subjects receiving 90–1,260 mg oral morphine equivalents per day enrolled and completed the study. Precipitated withdrawal occurred in 13% (2/15) of placebo-treated subjects and 47% (7/15) of buprenorphine-treated subjects. When combined with the 0.75 mg dose of buprenorphine, a 0.1 mg dose of naloxone increased the incidence of precipitated withdrawal to 60%, and a 0.2 mg dose of naloxone increased the incidence to 73%. By 15 minutes postdose, the mean change in Clinical Opioid Withdrawal Scale (COWS) score from predose was 3.0 for placebo, 6.9 for buprenorphine, 9.8 for BN 0.1 mg, and 12.4 for BN 0.2 mg. The mean COWS score with each active treatment was significantly greater than placebo (P<0.001), and the mean COWS score for each of the naloxone-containing treatments was significantly greater than for buprenorphine alone (P<0.001). Naloxone doses as low as 0.1 mg added an abuse-deterrent effect to a 0.75 mg IV dose of buprenorphine.

Below:  BBN with the BEMA^® technology.  Notes: BBN is an oral transmucosal dosage form of BN that uses the BEMA^® technology to optimize drug absorption and enhance patient convenience. The film adheres to the inside of the cheek within seconds, and the buprenorphine is efficiently absorbed. The backing layer creates a barrier to facilitate one-way absorption into the cheek. There is no need for patients to avoid talking or swallowing during administration, and the film completely dissolves. Abbreviations: BBN, BN buccal film; BN, buprenorphine–naloxone; BEMA^®, BioErodible MucoAdhesive.

Below:  Subjects requiring rescue medication.  Note: Includes 15-minute scores for subjects who did not rescue.  Abbreviation: BN, buprenorphine–naloxone.

Full article at:   http://goo.gl/Bf0O3w

By:  Lynn R Webster,1 Michael D Smith,1 Cemal Unal,2 and Andrew Finn3

¹PRA Health Sciences, Salt Lake City, UT, USA

²Biometrical Solutions LLC, Raleigh, NC, USA

³BioDelivery Sciences International, Inc., Raleigh, NC, USA

Correspondence: Lynn R Webster, PRA Health Sciences, 3838 South 700 East #202, Salt Lake City, UT 84106, USA, Tel +1 801 269 8200, Email moc.liamg@dmretsbewrl

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