Basic pharmacology of buprenorphine

Buprenorphine is a derivative of the morphine alkaloid thebaine. The plasma elimination half‐life of buprenorphine is three times longer than that of the active metabolite, norbuprenorphine. Although the elimination of norbuprenorphine from the body is more rapid than that of buprenorphine, the plasma concentration of norbuprenorphine was observed to exceed that of buprenorphine with chronic administration of buprenorphine. This plasma level of norbuprenorphine is based on the proportional increase in norbuprenorphine‐glucuronide observed after one enterohepatic circulation of buprenorphine due to the first‐pass metabolism. When buprenorphine and norbuprenorphine were administered intraventricularly, the analgesic effect of norbuprenorphine was approximately one‐fourth that of buprenorphine. After intravenous administration of buprenorphine or norbuprenorphine in rats, the analgesic effect of norbuprenorphine was approximately 1/50th that of buprenorphine. The remarkably weak analgesic effect of norbuprenorphine after intravenous administration may be due to the low permeability of norbuprenorphine into the brain. Therefore, the plasma concentration of norbuprenorphine with chronic administration of buprenorphine has little analgesic effect. The most dangerous side effect of opioid therapy is respiratory depression. In our study of the respiratory effects after intravenous infusion in rats, norbuprenorphine was ten times more potent than the parent drug. However, it is possible that the plasma levels of norbuprenorphine with chronic administration of buprenorphine are not sufficiently high to depress respiratory function. Overall, buprenorphine is a safe and highly effective analgesic opioid for the treatment of chronic pain.