Picture of Buprenorphine molecule

Buprenorphine

Chemical Name:
17-(cyclopropylmethyl)-alpha-(1,1-dimethylethyl)-4,5-epoxy- 18,19-dihydro-3-hydroxy-6-methoxy-alpha-methyl-6,14- ethenomorphinan-7-methanol
Classification:
Partial opioid agonist
Primary Uses:
Opiate dependency treatment, analgesia
Brand Names:
Suboxone, Subutex, Buprenex, Temgesic
Slang:
Bupe, subs, subbies, orange guys

General Information

Buprenorphine, a partial opioid agonist, is a chemical derivative of thebaine. During the 1980s, Reckitt & Colman began marketing buprenorphine hydrochloride under the name Buprenex. Buprenex is primarily found in 0.324 mg/ml injectable formulations. 0.324 mg buprenorphine hydrochloride is equivalent to 0.3 mg buprenorphine. On October 7th 2002, the DEA rescheduled the drug from Schedule V to Schedule III. A day later, the FDA approved the drug as a treatment for opiate/opioid addiction, under the brand names Suboxone and Subutex. Two street names for the buprenorphine/naloxone compound are "bupe" and "sub(s)."

Pharmacology & Pharmacokinetics

Buprenorphine has a very high binding affinity to the mu-opioid receptor; however, due to the fact that it is only a partial opioid agonist, it does not produce the same "high" or "rush" of full agonists (morphine, oxycodone, heroin). These two properties must be carefully considered in any given situation for two reasons. Most importantly, the long half-life and high binding affinity can complicate situations involving overdosage. For individuals dependent on full-agonist opioids, if there is not sufficient time between the last dose of the full-agonist and the dosing of buprenorphine, it can trigger precipitated withdrawal.

Buprenorphine or buprenorphine hydrochloride can be administered via intravenous or intramuscular injection, transdermally with a patch, or in the form of a sublingual tablet. The drug is broken down into norbuprenorphine, which is an active metabolite, and glucuronidation. This is completed via N-dealkylation mediated by cytochrome P-450 3A4 isozyme. The average elimination half-life of buprenorphine is 37 hours.

Method of Administration Bioavailability Peak Plasma Half-Life
Sublingual 13 - 51.4% 2 hours 37 hours
Intraarterial 100%
Intravenous 98% 1.5 minutes < 37 hours
Intrahepatoportal 49%
Intraduodenal 9.7%
Buccal 27.8%

Legal Status

In the United States, this drug is a Schedule III substance, making it illegal to use or possess without a prescription. Schedule III substances, such as codeine, hydrocodone (when combined with a non-narcotic active ingredient), and Marinol (synthetic THC), meet the following criteria according to the Controlled Substances Act:

Side Effects

  • Pain relief
  • Sedation
  • Nausea
  • Vomiting
  • Dizziness
  • Headache
  • Constipation
  • Sweating
  • Insomnia
  • Urinary retention
  • Miosis
  • Confusion
  • Euphoria or dysphoria

Withdrawal

Don't let anyone fool you, even buprenorphine, the active ingredient in Suboxone, comes equipped with an unpleasant withdrawal syndrome; however, buprenorphine withdrawal is generally milder than that which is experienced from full agonist. Buprenorphine must be tapered slowly due to its long half-life, which can cause withdrawal to kick in later than with the traditional fast-acting opiates. Buprenorphine withdrawal symptoms can linger for a few months, which is why a slow, modest taper is preferred to a quicker taper. Below are some possible withdrawal symptoms:

  • Depression/dysphoric mood
  • Nausea and vomiting
  • Muscle aches and cramps
  • Insomnia
  • Mild fever
  • Lacrimation
  • Rhinorrhea
  • Profuse sweating
  • Piloerection
  • Diarrhea
  • Frequent yawning
  • Drug craving


Sources

[1] Mendelson J, Upton RA, Everhart ET, Jacob P 3rd, Jones RT. Bioavailability of sublingual buprenorphine. J Clin Pharmacol [Entrez PubMed]. 1997 Jan;37(1):31-7.
[2] Brewster D, Humphrey MJ, Mcleavy MA. The systemic bioavailability of buprenorphine by various routes of administration. J Pharm Pharmacol [Entrez PubMed]. 1981 Aug;33(8):500-6.
[3] James J. Kuhlman, Jr., Shairose Lalani, Joseph Magluilo, Jr., Barry Levine, William D. Darwin, Rolley E. Johnson, and Edward J. Cone. Human Pharmacokinetics of Intravenous, Sublingual, and Buccal Buprenorphine. Journal of Analytical Toxicology, Volume 20, Number 6, October 1996, pp. 369-378.