Effect of buprenorphine on CYP3A activity in rat and human liver microsomes

Life Sci. 2000 Feb 25;66(14):1293-8. doi: 10.1016/s0024-3205(00)00436-7.


Buprenorphine is a partial opioid agonist available in France as an alternative to methadone in the treatment of opiate-dependent individuals. Twenty deaths have been reported in patients who have ingested buprenorphine in combination with benzodiazepines. Since buprenorphine and many benzodiazepines are CYP3A substrates, the effect of buprenorphine on CYP3A activity was examined in order to assess the likelihood of a pharmacokinetic interaction. The formation of 6beta-hydroxytestosterone was measured in dexamethasone-induced rat liver microsomes and in human liver microsomes under control conditions and in the presence of buprenorphine. Buprenorphine was found to be a weak inhibitor of CYP3A with a 50% decrease in enzyme activity occurring at a concentration of 118 microM (IC50) in human liver microsomes. IC50 was 0.3 microM for ketoconazole in the same system. Since the IC50 for buprenorphine is roughly 2000 times higher than typical plasma concentrations, this drug is unlikely to cause clinically significant inhibition of CYP3A in patients. Excessive CNS depression due to the combination of buprenorphine and benzodiazepines is most likely due to additive or synergistic pharmacologic effect unrelated to a pharmacokinetic interaction between the drugs.

MeSH terms

  • Animals
  • Antineoplastic Agents, Hormonal / pharmacology
  • Aryl Hydrocarbon Hydroxylases*
  • Buprenorphine / pharmacology*
  • Chromatography, High Pressure Liquid
  • Cytochrome P-450 CYP3A
  • Cytochrome P-450 Enzyme Inhibitors*
  • Dexamethasone / pharmacology
  • Enzyme Inhibitors / pharmacology*
  • Humans
  • Hydroxytestosterones / metabolism
  • In Vitro Techniques
  • Ketoconazole / pharmacology
  • Male
  • Microsomes, Liver / drug effects
  • Microsomes, Liver / enzymology*
  • Narcotics / pharmacology*
  • Oxidoreductases, N-Demethylating / antagonists & inhibitors*
  • Rats
  • Rats, Sprague-Dawley
  • Spectrophotometry, Ultraviolet


  • Antineoplastic Agents, Hormonal
  • Cytochrome P-450 Enzyme Inhibitors
  • Enzyme Inhibitors
  • Hydroxytestosterones
  • Narcotics
  • Buprenorphine
  • 6 beta-hydroxytestosterone
  • Dexamethasone
  • Aryl Hydrocarbon Hydroxylases
  • Cytochrome P-450 CYP3A
  • Oxidoreductases, N-Demethylating
  • Ketoconazole