Due to the mainly hepatic elimination,  no risk of accumulation exists in people with renal impairment.One of the major active metabolites of buprenorphine is norbuprenorphine, which, in contrast to buprenorphine itself, is a full agonist of the MOR, DOR, and ORL-1, and a partial agonist at the KOR. However, relative to buprenorphine, norbuprenorphine has extremely little antinociceptive potency (1/50th that of buprenorphine), but markedly depresses respiration (10-fold more than buprenorphine). This may be explained by very poor brain penetration of norbuprenorphine due to a high affinity of the compound for P-glycoprotein. In contrast to norbuprenorphine, buprenorphine and its glucuronide metabolites are negligibly transported by P-glycoprotein.The glucuronides of buprenorphine and norbuprenorphine are also biologically active, and represent major active metabolites of buprenorphine. Buprenorphine-3-glucuronide has affinity for the MOR (Ki = 4.9 pM), DOR (Ki = 270 nM) and ORL-1 (Ki = 36 μM), and no affinity for the KOR. It has a small antinociceptive effect and no effect on respiration. Norbuprenorphine-3-glucuronide has no affinity for the MOR or DOR, but does bind to the KOR (Ki = 300 nM) and ORL-1 (Ki = 18 μM). It has a sedative effect but no effect on respiration. Chemistry
Buprenorphine is a semisynthetic derivative of thebaine, and is fairly soluble in water, as its hydrochloride salt. It degrades in the presence of light. Detection in body fluids
Buprenorphine and norbuprenorphine may be quantified in blood or urine to monitor use or non-medical recreational use, confirm a diagnosis of poisoning, or assist in a medicolegal investigation.
Pharmacology
Pharmacodynamics
Opioid receptor modulator
Buprenorphine has been reported to possess these following pharmacological activities:
μ-Opioid receptor (MOR): Very high affinity partial agonist: at low doses, the MOR-mediated effects of buprenorphine are comparable to those of other narcotics, but these effects reach a "ceiling" as the receptor population is saturated. This behavior is responsible for several unique properties: buprenorphine greatly reduces the effect of most other MOR agonists, can cause precipitated withdrawal when used in actively opioid dependent persons, and has a lower incidence of respiratory depression and fatal overdose relative to full MOR agonists. κ-Opioid receptor (KOR): High affinity antagonist—this activity is hypothesized to underlie some of the effects of buprenorphine on mood disorders and addiction. δ-Opioid receptor (DOR): High affinity antagonist
Nociceptin receptor (NOP, ORL-1): Weak affinity, very weak partial agonistIn simplified terms, buprenorphine can essentially be thought of as a nonselective, mixed agonist–antagonist opioid receptor modulator, acting as an unusually high affinity weak partial agonist of the MOR, a high affinity antagonist of the KOR and DOR, and a relatively low affinity, very weak partial agonist of the ORL-1/NOP.Although buprenorphine is a partial agonist of the MOR, human studies have found that it acts like a full agonist with respect to analgesia in opioid-intolerant individuals.