CLINICAL PHARMACOLOGY
Buprenorphine HCl is a parenteral opioid analgesic with 0.3 mg buprenorphine being approximately equivalent to 10 mg morphine sulfate in analgesic and respiratory depressant effects in adults. Pharmacological effects occur as soon as 15 minutes after intramuscular injection and persist for 6 hours or longer. Peak pharmacologic effects usually are observed at 1 hour. When used intravenously, the times to onset and peak effect are shortened.
The limits of sensitivity of available analytical methodology precluded demonstration of bioequivalence between intramuscular and intravenous routes of administration. In postoperative adults, pharmacokinetic studies have shown elimination half-lives ranging from 1.2 to 7.2 hours (mean 2.2 hours) after intravenous administration of 0.3 mg of buprenorphine. A single, ten-patient, pharmacokinetic study of doses of 3 mcg/kg in children (age 5 to 7 years) showed a high inter-patient variability, but suggests that the clearance of the drug may be higher in children than in adults. This is supported by at least one repeat-dose study in postoperative pain that showed an optimal inter-dose interval of 4 to 5 hours in pediatric patients as opposed to the recommended 6 to 8 hours in adults.
Buprenorphine, in common with morphine and other phenolic opioid analgesics, is metabolized by the liver and its clearance is related to hepatic blood flow. Studies in patients anesthetized with 0.5% halothane have shown that this anesthetic decreases hepatic blood flow by about 30%.
Mechanism of Analgesic Action
Buprenorphine HCl exerts its analgesic effect via high affinity binding to m subclass opiate receptors in the central nervous system. Although buprenorphine HCl may be classified as a partial agonist, under the conditions of recommended use it behaves very much like classical m agonists such as morphine. One unusual property of buprenorphine HCl observed in in vitro studies is its very slow rate of dissociation from its receptor. This could account for its longer duration of action than morphine, the unpredictability of its reversal by opioid antagonists, and its low level of manifest physical dependence.
Narcotic Antagonist Activity
Buprenorphine demonstrates narcotic antagonist activity and has been shown to be equipotent with naloxone as an antagonist of morphine in the mouse tail flick test.
Cardiovascular Effects
Buprenorphine HCl may cause a decrease or, rarely, an increase in pulse rate and blood pressure in some patients.
Effects on Respiration
Under usual conditions of use in adults, both buprenorphine HCl and morphine show similar dose-related respiratory depressant effects. At adult therapeutic doses, buprenorphine HCl (0.3 mg buprenorphine) can decrease respiratory rate in an equivalent manner to an equianalgesic dose of morphine (10 mg). (See WARNINGS.)
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