From Wikipedia, the free encyclopedia
  (Redirected from Butrans)
Jump to: navigation, search
Systematic (IUPAC) name
Clinical data
Trade names Buprenex, Subutex, Suboxone, Butrans
AHFS/Drugs.com monograph
MedlinePlus a605002
Pregnancy cat. C (AU) C (US)
Legal status Controlled (S8) (AU) Class C (UK) Schedule III (USA)

sublingual, IM, IV, transdermal, intranasal, rectally

Pharmacokinetic data
Bioavailability 55%(sublingual)[1]/48.2% +/- 8.35%(intranasal)[2]
Protein binding 96%
Metabolism hepatic
Half-life 20–70, mean 37 hours
Excretion biliary and renal
CAS number 52485-79-7 YesY
ATC code N02AE01 N07BC01
PubChem CID 644073
IUPHAR ligand 1670
DrugBank DB00921
ChemSpider 559124 YesY
KEGG D07132 YesY
Chemical data
Formula C29H41NO4 
Mol. mass 467.64 g/mol
 N (what is this?)  (verify)
Suboxone tablet

Buprenorphine is a semi-synthetic partial opioid agonist that is used to treat opioid addiction in higher dosages, to control moderate acute pain in non-opioid-tolerant individuals in lower dosages and to control moderate chronic pain in even smaller doses.[3] It is available in a variety of formulations: Subutex, Suboxone, Zubsolv (buprenorphine HCl and/or naloxone HCl; typically used for opioid addiction), Temgesic (sublingual tablets for moderate to severe pain), Buprenex (solutions for injection often used for acute pain in primary-care settings), Norspan and Butrans (transdermal preparations used for chronic pain).[4]

In the European Union, Suboxone and Subutex, buprenorphine's high-dose sublingual tablet preparations, were approved for opioid addiction treatment in September 2006.[5] In the Netherlands, buprenorphine is a List II drug of the Opium Law, though special rules and guidelines apply to its prescription and dispensation. In the United States, it was rescheduled to Schedule III drug from Schedule V just before FDA approval of Suboxone and Subutex.[6] In recent years, buprenorphine has been introduced in most European countries as a transdermal formulation for the treatment of chronic pain.

Medical uses[edit]

Its primary uses in medicine are in the treatment of those addicted to opioids, especially heroin, but it may also be used to treat pain; most often in transdermal patch form.[3]

Buprenorphine versus methadone[edit]

Buprenorphine has the advantage of being a partial agonist; hence negating the potential for life-threatening respiratory depression in cases of abuse.[4] Studies show the effectiveness of buprenorphine and methadone are almost identical, along with the statistical likeliness of any adverse effects except for more sedation among methadone users. At low doses from 2 to 6 mg, however, suboxone has a lower retention rate than low doses from 40 mg or less of methadone.[7]

Inpatient rehabilitation and detoxification[edit]

The treatment phase begins once the person is stabilised and receives medical clearance. This portion of treatment comprises multiple therapy sessions, which include both group and individual counselling with various chemical dependency counsellors, psychologists, psychiatrists, social workers, and other professionals. In addition, many treatment centres utilise twelve-step facilitation techniques, embracing the 12-step programs practised by such organizations as Alcoholics Anonymous and Narcotics Anonymous. Some people on maintenance therapies have veered away from such organizations as Narcotics Anonymous, instead opting to create their own twelve-step fellowships (such as Methadone Anonymous) or depart entirely from the twelve-step model of recovery (using a program such as SMART Recovery).[8][9]

Suboxone and naloxone[edit]

Suboxone (a controlled substance) contains buprenorphine as well as the opioid antagonist naloxone to deter the abuse of tablets by intravenous injection. Even though controlled trials in human subjects suggest that buprenorphine and naloxone at a 4:1 ratio will produce unpleasant withdrawal symptoms if taken intravenously by people who are addicted to opioids, these studies administered buprenorphine/naloxone to people already addicted to less powerful opiates such as morphine.[10][11][12][13][14] These studies show the strength of buprenorphine/naloxone in displacing opiates, but do not show the effectiveness of naloxone displacing buprenorphine and causing withdrawal. The Suboxone formulation still has potential to produce an opioid agonist "high" if injected by non-dependent persons, which may provide some explanation to street reports indicating that the naloxone is an insufficient deterrent to injection of suboxone.[15][16] The addition of naloxone and the reasons for it are conflicting. Published data clearly shows the Ki or binding affinity of buprenorphine is 0.2157 nM, while that for naloxone is 1.1518 nM.[17] Furthermore, the IC50 or the half maximal inhibitory concentration for buprenorphine to displace naloxone is 0.52 nM, while the IC50s of other opiates in displacing buprenorphine, is 100 to 1,000 times greater.[18] These studies help explain the ineffectiveness of naloxone in preventing suboxone abuse, as well as the potential dangers of overdosing on buprenorphine, as naloxone is not strong enough to reverse its effects.

Investigational uses[edit]

Antidepressant potential[edit]

A clinical trial conducted at Harvard Medical School in the mid-1990s demonstrated that a majority of unipolar non-psychotic persons with major depression refractory to conventional antidepressants and electroconvulsive therapy could be successfully treated with buprenorphine.[19][20][21][22][23][24][25] Clinical depression is currently not an approved indication for the use of any opioid, but some doctors are realizing its potential as an antidepressant in cases where the person cannot tolerate or is resistant to conventional antidepressants.

Neonatal abstinence[edit]

Buprenorphine has been used in the treatment of the neonatal abstinence syndrome,[26] a condition in which newborns exposed to opioids during pregnancy demonstrate signs of withdrawal.[27] Use currently is limited to infants enrolled in a clinical trial conducted under an FDA approved investigational new drug (IND) application.[28] An ethanolic formulation used in neonates is stable at room temperature for at least 30 days.[29]

Physicochemical properties[edit]

It is a semi-synthetic analogue of thebaine[30] and is fairly insoluble in water, as its hydrochloride salt.[4] It also degrades in the presence of light.[4]


Buprenorphine is metabolised by the liver, via CYP3A4 (also CYP2C8 seems to be involved) isozymes of the cytochrome P450 enzyme system, into norbuprenorphine (by N-dealkylation). The glucuronidation of buprenorphine is primarily carried out by UGT1A1 and UGT2B7, and that of norbuprenorphine by UGT1A1 and UGT1A3. These glucuronides are then eliminated mainly through excretion into the bile. The elimination half-life of buprenorphine is 20–73 hours (mean 37). Due to the mainly hepatic elimination, there is no risk of accumulation in people with renal impairment.[31]

Buprenorphine's main active metabolite, norbuprenorphine, is a μ-opioid, δ-opioid, and nociceptin receptor full agonist, as well as a κ-opioid receptor partial agonist.[32][33] Due to these actions it is likely that buprenorphine would antagonise its effects.

The glucuronides are also biologically active.[34] Buprenorphine-3-glucuronide has affinity for the μ-opioid receptor(Ki = 4.9±2.7 pM), δ-opioid receptor (Ki = 270±0.4 nM) and the nociceptin receptor (Ki = 36±0.3 µM). It shows no affinity for the kappa opioid receptor. It has a small antinoceptive effect and no effect on respiration. Norbuprenorphine-3-glucuronide has no affinity for the mu or delta opioid receptor. It does however bind to the kappa opioid receptor (Ki = 300±0.5 nM) and the nociceptin receptor (Ki= 18±0.2 µM). It has a sedative effect but no effect on respiration.

Adverse effects[edit]

Common adverse drug reactions associated with the use of buprenorphine are similar to those of other opioids and include: nausea and vomiting, drowsiness, dizziness, headache, memory loss, cognitive and neural inhibition, perspiration, itchiness, dry mouth, miosis, orthostatic hypotension, male ejaculatory difficulty, decreased libido, and urinary retention. Constipation and CNS effects are seen less frequently than with morphine.[35] Hepatic necrosis and hepatitis with jaundice have been reported with the use of buprenorphine, especially after intravenous injection of crushed tablets.[citation needed]

The most severe and serious adverse reaction associated with opioid use in general is respiratory depression, the mechanism behind fatal overdose. Buprenorphine behaves differently than other opioids in this respect, as it shows a ceiling effect for respiratory depression.[35] Moreover, former doubts on the antagonisation of the respiratory effects by naloxone have been disproved: Buprenorphine effects can be antagonised with a continuous infusion of naloxone.[36] Concurrent use of buprenorphine and CNS depressants (such as alcohol or benzodiazepines) is contraindicated as it may lead to fatal respiratory depression. Benzodiazepines, in prescribed doses, are not contraindicated in individuals tolerant to either opioids or benzodiazepines.

Detection in biological fluids[edit]

Buprenorphine and norbuprenorphine (the major active metabolite of buprenorphine) may be quantitated in blood or urine to monitor use or abuse, confirm a diagnosis of poisoning, or assist in a medicolegal investigation. There is a significant overlap of drug concentrations in body fluids within the possible spectrum of physiological reactions ranging from asymptomatic to comatose. Therefore it is critical to have knowledge of both the route of administration of the drug and the level of tolerance to opioids of the individual when results are interpreted.[37]

See also[edit]


  1. ^ Weinberg, D. S.; Inturrisi, C. E.; Reidenberg, B.; Moulin, D. E.; Nip, T. J.; Wallenstein, S.; Houde, R. W.; Foley, K. M. (1988). "Sublingual absorption of selected opioid analgesics". Clinical pharmacology and therapeutics 44 (3): 335–342. PMID 2458208.  edit
  2. ^ Eriksen, J.; Jensen, N. H.; Kamp-Jensen, M.; Bjarnø, H.; Friis, P.; Brewster, D. (1989). "The systemic availability of buprenorphine administered by nasal spray". The Journal of pharmacy and pharmacology 41 (11): 803–805. PMID 2576057.  edit
  3. ^ a b Rossi, S, ed. (2013). Australian Medicines Handbook (2013 ed.). Adelaide: The Australian Medicines Handbook Unit Trust. ISBN 978-0-9805790-9-3.  edit
  4. ^ a b c d "Buprenorphine". Martindale: The Complete Drug Reference. London, UK: Pharmaceutical Press. 14 January 2014. Retrieved 6 April 2014. 
  5. ^ Suboxone EU Approval
  6. ^ DEA Rescheduling
  7. ^ Mattick, RP; Kimber, J; Breen, C; Davoli, M (February 2014). "Buprenorphine maintenance versus placebo or methadone maintenance for opioid dependence." (PDF). The Cochrane Database of Systematic Reviews (2): CD002207. doi:10.1002/14651858.CD002207.pub3. 
  8. ^ Glickman L, Galanter M, Dermatis H, Dingle S (December 2006). "Recovery and spiritual transformation among peer leaders of a modified methadone anonymous group". J Psychoactive Drugs 38 (4): 531–3. doi:10.1080/02791072.2006.10400592. PMID 17373569. 
    Gilman SM, Galanter M, Dermatis H (December 2001). "Methadone Anonymous: A 12-Step Program for Methadone Maintained Heroin Addicts". Subst Abus 22 (4): 247–256. doi:10.1080/08897070109511466. PMID 12466684. 
    McGonagle D (October 1994). "Methadone anonymous: a 12-step program. Reducing the stigma of methadone use". J Psychosoc Nurs Ment Health Serv 32 (10): 5–12. PMID 7844771. 
  9. ^ Horvath, A. Thomas (2000). Journal of Rational-Emotive and Cognitive-Behavior Therapy 18 (3): 181–191. doi:10.1023/A:1007831005098. 
  10. ^ Mendelson, J.; Jones, R. T.; Fernandez, I.; Welm, S.; Melby, A. K.; Baggott, M. J. (1996). "Buprenorphine and naloxone interactions in opiate-dependent volunteers*". Clinical Pharmacology & Therapeutics 60 (1): 105–114. doi:10.1016/S0009-9236(96)90173-3. PMID 8689806.  edit
  11. ^ Fudala, PJ; Yu, E; MacFadden, W; Boardman, C; Chiang, CN (1998). "Effects of buprenorphine and naloxone in morphine-stabilized opioid addicts". Drug and Alcohol Dependence 50 (1): 1–8. doi:10.1016/S0376-8716(98)00008-8. PMID 9589267. 
  12. ^ Stoller, K. B.; Bigelow, G. E.; Walsh, S. L.; Strain, E. C. (2001). "Effects of buprenorphine/naloxone in opioid-dependent humans". Psychopharmacology 154 (3): 230–242. PMID 11351930.  edit
  13. ^ Strain, E. C.; Preston, K. L.; Liebson, I. A.; Bigelow, G. E. (1992). "Acute effects of buprenorphine, hydromorphone and naloxone in methadone-maintained volunteers". The Journal of pharmacology and experimental therapeutics 261 (3): 985–993. PMID 1376362.  edit
  14. ^ Harris, D. S.; Jones, R. T.; Welm, S.; Upton, R. A.; Lin, E.; Mendelson, J. (2000). "Buprenorphine and naloxone co-administration in opiate-dependent patients stabilized on sublingual buprenorphine". Drug and Alcohol Dependence 61 (1): 85–94. doi:10.1016/S0376-8716(00)00126-5. PMID 11064186.  edit
  15. ^ Strain, E. C.; Stoller, K.; Walsh, S. L.; Bigelow, G. E. (2000). "Effects of buprenorphine versus buprenorphine/naloxone tablets in non-dependent opioid abusers". Psychopharmacology 148 (4): 374–383. PMID 10928310.  edit
  16. ^ Clinical Guidelines for the Use of Buprenorphine in the Treatment of Opioid Addiction. Treatment Improvement Protocol (TIP) 40. Laura McNicholas. US Department of Health and Human Services.
  17. ^ Volpe, D. A.; Tobin, G. A. M.; Mellon, R. D.; Katki, A. G.; Parker, R. J.; Colatsky, T.; Kropp, T. J.; Verbois, S. L. (2011). "Uniform assessment and ranking of opioid Mu receptor binding constants for selected opioid drugs". Regulatory Toxicology and Pharmacology 59 (3): 385–390. doi:10.1016/j.yrtph.2010.12.007. PMID 21215785.  edit
  18. ^ Villiger, J. W.; Taylor, K. M. (1981). "Buprenorphine : Characteristics of binding sites in the rat central nervous system". Life sciences 29 (26): 2699–2708. doi:10.1016/0024-3205(81)90529-4. PMID 6276633.  edit
  19. ^ Bodkin, JA; Zornberg, GL; Lukas, SE; Cole, JO (1995). "Buprenorphine treatment of refractory depression". Journal of Clinical Psychopharmacology 15 (1): 49–57. doi:10.1097/00004714-199502000-00008. PMID 7714228. 
  20. ^ Emrich, H. M.; Vogt, P.; Herz, A. (1982). "Possible antidepressive effects of opioids: Action of buprenorphine". Annals of the New York Academy of Sciences 398: 108–112. PMID 6760767.  edit
  21. ^ Emrich, HM (1984). "Endorphins in psychiatry". Psychiatr Dev 2 (2): 97–114. PMID 6091098. 
  22. ^ Mongan, L; Callaway, E (1990). "Buprenorphine responders". BiolPsychiatry 28 (12): 1078–1080. PMID 2289007. 
  23. ^ Nyhuis, P. W.; Gastpar, M. (2005). "Opiate treatment in ECT-resistant depression". Pharmacopsychiatry 38 (5). doi:10.1055/s-2005-918797.  edit
  24. ^ Nyhuis, PW; Specka, M.; Gastpar, M. (2006). "Does the antidepressive response to opiate treatment describe a subtype of depression ?". European Neuropsychopharmacology 16 (S16): S309. doi:10.1016/S0924-977X(06)70328-5. Retrieved 21 September 2012. 
  25. ^ Nyhuis, P. W.; Gastpar, M.; Scherbaum, N. (2008). "Opiate Treatment in Depression Refractory to Antidepressants and Electroconvulsive Therapy". Journal of Clinical Psychopharmacology 28 (5): 593–595. doi:10.1097/JCP.0b013e31818638a4. PMID 18794671.  edit
  26. ^ Kraft, WK; Gibson, E; Dysart, K; Damle, VS; Larusso, JL; Greenspan, JS; Moody, DE; Kaltenbach, K; Ehrlich, ME (September 2008). "Sublingual buprenorphine for treatment of neonatal abstinence syndrome: a randomized trial". Pediatrics 122 (3): e601–7. doi:10.1542/peds.2008-0571. PMC 2574639. PMID 18694901. 
  27. ^ Kraft, W. K.; Van Den Anker, J. N. (2012). "Pharmacologic Management of the Opioid Neonatal Abstinence Syndrome". Pediatric Clinics of North America 59 (5): 1147–1165. doi:10.1016/j.pcl.2012.07.006. PMID 23036249.  edit
  28. ^ Buprenorphine for the Treatment of Neonatal Abstinence Syndrome. Clinicaltrials.gov. NCT00521248. Retrieved on 2013-05-19.
  29. ^ Anagnostis, E. A.; Sadaka, R. E.; Sailor, L. A.; Moody, D. E.; Dysart, K. C.; Kraft, W. K. (2011). "Formulation of buprenorphine for sublingual use in neonates". The journal of pediatric pharmacology and therapeutics : JPPT : the official journal of PPAG 16 (4): 281–284. doi:10.5863/1551-6776-16.4.281. PMC 3385042. PMID 22768012.  edit
  30. ^ Heel, RC; Brogden, RN; Speight, TM; Avery, GS (February 1979). "Buprenorphine: a review of its pharmacological properties and therapeutic efficacy.". Drugs 17 (2): 81–110. doi:10.2165/00003495-197917020-00001. PMID 378645. 
  31. ^ Moody, D. E.; Fang, W. B.; Lin, S. -N.; Weyant, D. M.; Strom, S. C.; Omiecinski, C. J. (2009). "Effect of Rifampin and Nelfinavir on the Metabolism of Methadone and Buprenorphine in Primary Cultures of Human Hepatocytes". Drug Metabolism and Disposition 37 (12): 2323–2329. doi:10.1124/dmd.109.028605. PMC 2784702. PMID 19773542.  edit
  32. ^ Yassen A, Kan J, Olofsen E, Suidgeest E, Dahan A, Danhof M (2007). "Pharmacokinetic-pharmacodynamic modeling of the respiratory depressant effect of norbuprenorphine in rats". The Journal of Pharmacology and Experimental Therapeutics 321 (2): 598–607. doi:10.1124/jpet.106.115972. PMID 17283225. 
  33. ^ Huang, P.; Kehner, G. B.; Cowan, A.; Liu-Chen, L. Y. (2001). "Comparison of pharmacological activities of buprenorphine and norbuprenorphine: Norbuprenorphine is a potent opioid agonist". The Journal of pharmacology and experimental therapeutics 297 (2): 688–695. PMID 11303059.  edit
  34. ^ Brown, SM; et al. "Buprenorphine metabolites, buprenorphine-3-glucuronide and norbuprenorphine-3-glucuronide, are biologically active". Anesthesiology (2011). 
  35. ^ a b Budd K, Raffa RB. (eds.) Buprenorphine – The unique opioid analgesic. Thieme, 200, ISBN 3-13-134211-0
  36. ^ Van Dorp, E; Yassen, A; Sarton, E; Romberg, R; Olofsen, E; Teppema, L; Danhof, M; Dahan, A (2006). "Naloxone reversal of buprenorphine-induced respiratory depression". Anesthesiology 105 (1): 51–7. doi:10.1097/00000542-200607000-00012. PMID 16809994. 
  37. ^ Baselt, R. (2008) Disposition of Toxic Drugs and Chemicals in Man, 8th edition, Biomedical Publications, Foster City, CA, pp. 190–192, ISBN 0962652377.

External links[edit]