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Buprenorphine

Clinical Pharmacokinetics in the Treatment of Opioid Dependence

Clinical Pharmacokinetics Aims and scope Submit manuscript

Abstract

Buprenorphine is a semi-synthetic opioid derived from thebaine, a naturally occurring alkaloid of the opium poppy, Papaver somniferum. The pharmacology of buprenorphine is unique in that it is a partial agonist at the opioid μ receptor. Buprenorphine undergoes extensive first-pass metabolism and therefore has very low oral bioavailability; however, its bioavailability sublingually is extensive enough to make this a feasible route of administration for the treatment of opioid dependence. The mean time to maximum plasma concentration following sublingual administration is variable, ranging from 40 minutes to 3.5 hours. Buprenorphine has a large volume of distribution and is highly protein bound (96%). It is extensively metabolised by N-dealkylation to norbuprenorphine primarily through cytochrome P450 (CYP) 3A4. The terminal elimination half-life of buprenorphine is long and there is considerable variation in reported values (mean values ranging from 3 to 44 hours). Most of a dose of buprenorphine is eliminated in the faeces, with approximately 10–30% excreted in urine. Naloxone has been added to a sublingual formulation of buprenorphine to reduce the abuse liability of the product. The presence of naloxone does not appear to influence the pharmacokinetics of buprenorphine. Buprenorphine crosses the placenta during pregnancy and also crosses into breast milk. Buprenorphine dosage does not need to be significantly adjusted in patients with renal impairment; however, since CYP3A activity may be decreased in patients with severe chronic liver disease, it is possible that the metabolism of buprenorphine will be altered in these patients. Although there is limited evidence in the literature to date, drugs that are known to inhibit or induce CYP3A4 have the potential to diminish or enhance buprenorphine N-dealkylation. It appears that the interaction between buprenorphine and benzodiazepines is more likely to be a pharmacodynamic (additive or synergistic) than a pharmacokinetic interaction. The relationship between buprenorphine plasma concentration and response in the treatment of opioid dependence has not been well studied.

The pharmacokinetic and pharmacodynamic properties of buprenorphine allow it to be a feasible option for substitution therapy in the treatment of opioid dependence.

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Table I

Notes

  1. The use of trade names is for product identification purposes only and does not imply endorsement.

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Elkader, A., Sproule, B. Buprenorphine. Clin Pharmacokinet 44, 661–680 (2005). https://doi.org/10.2165/00003088-200544070-00001

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