Buprenorphine

Buprenorphine is a medication to treat opioid dependence. It was approved by the U.S. Food and Drug Administration on October 8, 2002, as a Schedule III narcotic (i.e., it has abuse potential and it is used as a medicine in the United States). This entry describes the pharmacology of buprenorphine, available types, and the drug's safety and efficacy. Buprenorphine is expected to increase access to opioid addiction treatment for an estimated 379,000 current illicit opioid (i.e., heroin) users and approximately 2 million problem users of prescription opi-oids as reported by the 2005 National Survey on Drug Use and Health.

As a medication that can be prescribed to patients under the Drug Addiction Treatment Act of 2000 (DATA 2000), buprenorphine provides an alternative to patients who are not able to access methadone clinics or who do not meet criteria for treatment in an outpatient treatment program (e.g., patient criteria for methadone treatment clinics often include opioid dependence for 1 or more years). As reviewed by Johnson and colleagues, buprenorphine has unique pharmacological characteristics that provide for a wide margin of safety and long duration of action. Buprenorphine is a partial agonist at the mu-opioid receptor and antagonist at the kappa-opioid receptor. As a partial agonist at the mu-opioid receptor, buprenorphine does not activate the mu-receptor to the same extent as does a full mu-opioid agonist (e.g., methadone), resulting in less than maximal opioid effect (also called a ceiling or plateau effect). Buprenorphine also binds tightly to the mu-receptor, allowing it to displace other opioids (e.g., methadone) [Page 147]from the receptor. Once it occupies the receptor, buprenorphine blocks the effects of other opioids for the mu-opioid receptor. Buprenorphine also disassociates or leaves the mu-opioid receptor slowly and this is thought to account for its long duration of action in the treatment of opioid dependence. It is this partial agonist activity at the mu-receptor, combined with its strong binding to the receptor site, that is believed to be responsible for buprenorphine's ability to block the effects of opioids (e.g., morphine, hydromorphone, heroin). Buprenorphine also has high affinity for, and antagonist action, at the kappa-receptor. As an antagonist at the kappa-receptor, buprenorphine may block increased kappa activity associated with opioid agonist withdrawal and lead to less dysthymia and increased positive mood and feelings. For the purpose of opioid-dependence treatment, the effects produced by buprenorphine at the mu-opioid receptor are the most important. In addition to buprenorphine's unique pharmacology, the safety profile (i.e., less respiratory depression and less overdose risk) for buprenorphine is greater than that of a full mu-opioid agonist (e.g., morphine, heroin, methadone, oxycodone). Additionally, buprenorphine has been reported to have less autonomie associated signs and symptoms of opioid withdrawal upon cessation.

There are two formulations of buprenorphine: a buprenorphine hydrogen chloride (HC1) tablet (Subutex) and a buprenorphine HC1 plus naloxone salt combination tablet (Suboxone). As discussed by Mendelson and Jones, Suboxone with a 4:1 buprenor-phine-to-naloxone ratio was developed because buprenorphine alone has abuse potential and is abused in many countries. Naloxone is poorly absorbed sub-lingually; however, when injected into the vein, naloxone can produce a precipitated opioid withdrawal syndrome in persons addicted to full mu-opioid agonists. The addition of naloxone in Suboxone is expected to reduce the abuse liability of buprenorphine alone. These unique characteristics allow for buprenorphine to be used both in new (e.g., office-based practice) and more traditional opioid treatment programs, thus providing opioid-dependent patients greater access to treatment.

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