Blockade of hydromorphone effects by buprenorphine/naloxone and buprenorphine

Buprenorphine is an opioid agonist-antagonist used in the treatment of opioid dependence. Naloxone has been combined with buprenorphine to decrease the parenteral abuse potential of buprenorphine. This addition of naloxone may also confer further opioid blockade efficacy.

To test the opioid blockade efficacy of sublingual buprenorphine/naloxone versus buprenorphine alone and determine whether: (1) the blockade efficacy of buprenorphine/naloxone varies between the time of expected maximal and minimal effects of naloxone, (2) the blockade efficacy of buprenorphine/naloxone and buprenorphine varies as a function of maintenance dose level, and (3) there are adaptive changes over time associated with repeated daily dosing of buprenorphine/naloxone and buprenorphine.

Residential subjects ( n=6) were maintained on different double-blind dose levels of buprenorphine/naloxone (4/1, 8/2, 16/4, 32/8 mg) and buprenorphine (32 mg) for 6-day periods and challenged with parenteral doses of hydromorphone (12 mg) in laboratory sessions.

There was no evidence of additional opioid blockade efficacy conferred by combining naloxone with buprenorphine. Higher doses of buprenorphine/naloxone provided greater blockade of hydromorphone effects. Changes over time associated with repeated daily dosing of buprenorphine/naloxone and buprenorphine were minimal.

The addition of naloxone to buprenorphine may deter the parenteral abuse of buprenorphine/naloxone, but it does not enhance the therapeutic efficacy of buprenorphine. The blockade efficacy of buprenorphine/naloxone is dose related; however, doses up to 32/8 mg buprenorphine/naloxone provide only partial blockade when subjects receive a high dose of an opioid agonist.