Pharmacotherapeutic group: Opioid analgesics, oripavine derivatives
ATCvet code: QN02AE01

In summary buprenorphine is a potent, long-acting analgesic acting at opiate receptors in the central nervous system. Buprenorphine can potentiate the effects of other centrally-acting agents, but unlike most opiates, buprenorphine has, at clinical doses, only a limited sedative effect of its own.

Buprenorphine exerts its analgesic effect via high affinity binding to various subclasses of opiate receptors, particularly µ, in the central nervous system. At clinical dose levels for analgesia, buprenorphine binds to opiate receptors with high affinity and high receptor avidity, such that its dissociation from the receptor site is slow, as demonstrated in in vitro studies. This property of buprenorphine could account for its longer duration of activity when compared to morphine. In circumstances where excessive opiate agonist is already bound to opiate receptors, buprenorphine can exert a narcotic antagonistic activity as a consequence of its high-affinity opiate receptor binding, such that an antagonistic effect on morphine equivalent to naloxone has been demonstrated.

Buprenorphine has little effect on gastro-intestinal motility.

Buprenorphine is rapidly absorbed after intramuscular injection in various animal species and man. The substance is highly lipophilic and the volume of distribution in body compartments is large. Pharmacological effects (e.g. mydriasis) may occur within minutes of administration and signs of sedation normally appear by 15 minutes. Analgesic effects appear around 30 minutes after injection with peak effects usually being observed at about 1–1.5 hours.

Following intramuscular administration to cats, the mean terminal half-life was 6.3 hours and the clearance was 23 ml/kg/min, however, there was considerable inter-cat variability in pharmacokinetic parameters.

Following intravenous administration to dogs at a 20 μg/kg dose, the mean terminal half-life was 9 hours and the mean clearance was 24 ml/kg/min, however there is considerable inter-dog variability in pharmacokinetic parameters.

Combined pharmacokinetic and pharmacodynamic studies have demonstrated a marked delay between plasma concentrations and analgesic effect. Plasma concentrations of buprenorphine should not be used to formulate individual animal dosage regimens, which should be determined by monitoring of the patient’s response.

The major route of excretion in all species except the rabbit (where urinary excretion predominates) is the faeces. Buprenorphine undergoes N-dealkylation and glucuronide conjugation by the intestinal wall and the liver and its metabolites are excreted via the bile into the gastro-intestinal tract.

In tissue distribution studies carried out in rats and rhesus monkeys, the highest concentrations of drug-related material were observed in liver, lung and brain. Peak levels occurred rapidly and declined to low levels by 24 hours after dosing.

Protein binding studies in rats have shown that buprenorphine is highly bound to plasma proteins, principally to alpha and beta globulins.