Buprenorphine

Buprenorphine is a thebaine derivative, μ-receptor partial agonist, and similar in structure to morphine but approximately 33 times more potent. Whereas fentanyl dissociates rapidly from μ-receptors (half-life of 6.8 minutes), buprenorphine has a higher affinity and takes much longer to dissociate (half-life of 166 minutes). Its onset of action is slow, its peak effect may not occur until 3 hours, and its duration of effect is prolonged (>10 hours). The volume of distribution of buprenorphine is 2.8 L/kg and its clearance is 20 mL/kg/min. The metabolites of buprenorphine, buprenorphine-3-glucuronide and norbuprenorphine, are significantly less potent and have lower affinity for the μ-receptor.

The subjective effects (e.g., euphoria) of buprenorphine are similar to those of morphine. Buprenorphine produces respiratory depression with a ceiling after 0.15 to 1.2 mg in adults. Higher doses do not produce further respiratory depression and may actually result in increased ventilation (predominance of antagonistic actions).^[478] Reversal with naloxone is limited by high affinity for and slow dissociation from the μ-opioid receptor of buprenorphine. ^[479] Buprenorphine has been successfully used for premedication (0.3 mg IM), as the analgesic component in balanced anesthesia (4.5 to 12 µg/kg), and for postoperative pain control (0.3 mg IM).^[480] Buprenorphine, like the other agonist-antagonist compounds, is not acceptable as a sole anesthetic, and its receptor kinetic profile restricts its usefulness if other μ-agonists are used. Opioid withdrawal symptoms develop slowly (5 to 10 days) after buprenorphine is discontinued following long-term administration.