Assessment of naltrexone antagonism of buprenorphine

Background Buprenorphine (BUP), a semi‐synthetic opioid, has unique pharmacologic characteristics: high affinity, slow dissociation constant, and prolonged duration of effect. The possibility of reversing its effects was questioned. Naltrexone (NTX), a pure opioid antagonist, has a higher receptor affinity than naloxone and blocks agonist‐related effects for at least 24 hours. We assessed the efficacy of NTX in reversing the analgesic effects of BUP. Methods Randomized double‐blind placebo‐controlled cross‐over study including 12 healthy male volunteers. On three separate days they received either 0.15 mg/70 kg BUP iv followed 45 minutes later by 50 mg NTX po, or BUP followed by placebo (PBO), or PBO followed by NTX. Data were collected up to 8 hours after drug administration. Quantitative sensory testing using thermal and electrical stimulations (Viking IV, Madison USA) was performed. Pain tolerance (cold pressor test) was assessed. Results BUP markedly increased the nociceptive threshold (BUP‐PBO 54% vs 13% PBO‐NTX; p<0.05), and pain tolerance (BUP‐PBO 50% vs PBO‐NTX 2%; p<0.01). NTX reversed BUP antinociceptive effects (pain tolerance: 68.5% decrease of the AUC of BUP‐NTX compared to the AUC of BUP‐PBO; p=0.008). NTX shortened the duration of the antinociceptive effect (<6 h vs >8 h). Conclusions Naltrexone reverses the antinociceptive effects of buprenorphine. The late reversal is probably due to delayed absorption. Clinical Pharmacology & Therapeutics (2005) 77 , P9–P9; doi: 10.1016/j.clpt.2004.11.036