Buprenorphine SR Chemistry

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Common Name: Buprenorphine Hydrochloride

Chemical Name: 6,14-Ethenomorphinan-7-methanol, 17-(cyclopropylmethyl)- alpha-(1,1-dimethylethyl)-4,5-epoxy 18, 19-dihydro-3-hydroxy-6-methoxy-alpha-methyl-, hydrochloride, [5alpha, 7alpha (S)]

Buprenorphine is a thebaine derivative with powerful analgesia approximately twenty-five to forty times as potent as morphine, and its analgesic effect is due to partial agonist activity at μ-opioid receptors (i.e., when the molecule binds to a receptor, it is only partially activated in contrast to a full agonist such as morphine). Buprenorphine also has very high binding affinity for the μ receptor such that opioid receptor antagonists (e.g. naloxone) only partially reverse its effects.



Buprenorphine is metabolized by the liver, via CYP3A4(also CYP2C8seems to be involved) isozymes of the cytochrome P450enzyme system, into norbuprenorphine(by N-dealkylation). The glucuronidationof buprenorphine is primarily carried out by UGT1A1and UGT2B7, and that of norbuprenorphine by UGT1A1and UGT1A3. These glucuronides are then eliminated mainly through excretion into the bile. The elimination half-lifeof buprenorphine is 20–73 hours (mean 37). Due to the mainly hepatic elimination, there is no risk of accumulation in patients with renal impairment.5

Buprenorphine's main active metabolite, norbuprenorphine, is a μ-opioid, δ-opioid, and nociceptin receptor full agonist, with a κ-opioid receptor partial agonist. Buprenorphine antagonizes its effects.

In an unpublished study, three dogs administered 270 ug/kg subcutaneously had plasma concentrations that rose rapidly reaching average Cmax of 2.14 ng/mL at an average Tmax of 1 hour. Notably average plasma concentration remained over 1.0 ng/mL from under 1 hour to over 72 hours post injection.

A recently published study in the Journal of the American Association for Laboratory Animal Science, tested this sustained-release formulation of buprenorphine in rats for analgesic efficacy and plasma concentration over a 72-h time period. Rats were injected subcutaneously with either 1.2 mg/kg sustained-release formulation (Bup-SR), 0.2 mL/kg buprenorphine HCl (Bup-HCl) and tested in a thermal nociception model or a surgical postoperative pain model. In both models, Buprenorphine-SR showed evidence of providing analgesia for 2 to 3 d, reporting plasma concentrations of buprenorphine remaining over 1 ng/mL for 72 h after a single dose.6

A pilot study, conducted in domestic cats was designed to determine if the sustained release  

Buprenorphine SR™ formulation was equivalent to repeated doses of  transmucosal administration     of  the commercial preparation Buprenex™over a period  of 72 hours. Animals received either a single, subcutaneousinjection of Buprenorphine SR at a dose rate of 120ug/kg, or a transmucosal dose of buprenorphine HCl [Buprenex™] every 12 hours for 72 hours. Results from analysis of blood samples [obtained at 1, 4, 8, 12, 18, 24, 36, 48 and 72 hours], reported data showing that only the single-dosed Buprenorphine SR cats maintained therapeutic blood levels for 72 hours.7No visible injection site irritations or clinical side effects were reported within both test groups.


5.Moody DE; Fang Lin SN; Weyant DM; Strom SC and Omiecinski CJ  Effect of Rifampin and Nelfinavir on the Metabolism of Methadone and Buprenorphine in Primary Cultures of Human Hepatocytes. Drug Metab Dispos December 2009 37:2323-29

6. Foley PL; LiangH; Crichlow AR Evaluation of a sustained release formulation of buprenorphine for analgesia in rats. JAALAS Vol 50, No 2, March 2011, 198–204

7. Pilot Study: Comparison of the efficacy and adverse effects of sustained-release buprenorphine hydrochloride following subcutaneous administration and buprenorphine hydrochloride following oral transmucosal administration in cats undergoing ovariohysterectomy  Davina L. Catbagan, DVM, MS; Jessica M. Quimby, DVM; Khursheed R. Mama, DVM; Jessica K. Rychel, DVM; Patrice M. Mich, DVM, MS

8. Clinical Bulletin Buprenorphine in cats