Interaction of buprenorphine and its metabolite norbuprenorphine with cytochromes p450 in vitro.

@article{Zhang2003InteractionOB,
  title={Interaction of buprenorphine and its metabolite norbuprenorphine with cytochromes p450 in vitro.},
  author={Wenjian Zhang and Yamini Ramamoorthy and Rachel F. Tyndale and Edward Sellers},
  journal={Drug metabolism and disposition: the biological fate of chemicals},
  year={2003},
  volume={31 6},
  pages={
          768-72
        }
}
Buprenorphine is a thebaine derivative used in the treatment of heroin and other opiate addictions. In this study, the selective probe reactions for each of the major hepatic cytochromes P450 (P450s) were used to evaluate the effect of buprenorphine and its main metabolite norbuprenorphine on the activity of these P450s. The index reactions used were CYP1A2 (phenacetin O-deethylation), CYP2A6 (coumarin 7-hydroxylation), CYP2C9 (diclofenac 4'-hydroxylation), CYP2C19 (omeprazole 5-hydrxoylation… 

Figures and Tables from this paper

Effect of psychotropic medication on the in vitro metabolism of buprenorphine in human cDNA-expressed cytochrome P450 enzymes

Both midazolam and zolpidem showed a distinct inhibitory potency towards NBUP formation by CYP 3A4, implicating a decreased conversion of BUP when preincubated, which strongly suggests a metabolically activated component in inhibition.

Effect of nonspecific binding to microsomes and metabolic elimination of buprenorphine on the inhibition of cytochrome P4502D6.

It is concluded that nonspecific binding to microsomes of the inhibitor could affect the inhibitory potency against CYP2D6 and a more precise estimate of the risk of adverse drug interaction could be achieved.

Inhibition of CYP2D6-mediated tramadol O-demethylation in methadone but not buprenorphine maintenance patients.

As the degree of opioid analgesia is largely dependent on M1 formation, methadone maintenance patients may not receive adequate analgesia from oral tramadol, and alternative analgesics whose metabolism is independent of CYP2D6 should be utilized in this patient population.

Quantitative Prediction of Cytochrome P450 (CYP) 2D6-Mediated Drug Interactions

Predictive distributions for 615 possible interactions were obtained, giving detailed information on some drugs or inhibitors that have been poorly studied so far, such as metoclopramide, bupropion and terbinafine.

Methadone: a review of drug-drug and pathophysiological interactions

This work set out to describe drug-drug interactions as well as physiological and pathophysiological factors that may impact the pharmacokinetics of methadone, and conducted a systematic search for papers and related abstracts published between 1966 and 2010.

Effects of HCV seropositive status on buprenorphine pharmacokinetics in opioid-dependent individuals.

Findings suggest the potential for opioid toxicity among HCV-infected patients treated with buprenorphine/naloxone, and possible hepatotoxic effects related to increased bup Renorphine exposure.

Pharmacogenetics of analgesics: toward the individualization of prescription.

This review summarizes the available data on the pharmacokinetic and pharmacodynamic consequences of known polymorphisms of drug-metabolizing enzymes, drug transporters, drug targets and other nonopioid biological systems on central and peripheral analgesics.
...

References

SHOWING 1-10 OF 40 REFERENCES

Inhibition of human drug metabolizing cytochrome P450 by buprenorphine.

The effects of buprenorphine, a powerful mixed agonist/antagonist analgesic, on several cytochrome P450 isoform specific reactions in human liver microsomes were investigated and would not be predicted to cause clinically significant interactions with other CYP-metabolized drugs.

Evaluation of methoxsalen, tranylcypromine, and tryptamine as specific and selective CYP2A6 inhibitors in vitro.

Tranylcypromine [particularly R-(+) isomer], tryptamine, and methoxsalen are specific and relatively selective for CYP2A6 and may be useful in vivo to decrease smoking by inhibiting nicotine metabolism with a low risk of metabolic drug interactions.

Human buprenorphine N-dealkylation is catalyzed by cytochrome P450 3A4.

The demonstration of BN N-dealkylation by recombinant CYP3A4 and the agreement in the affinities (apparent KM values) of human liver microsomes and recombinant cytochrome P450 enzyme(s) provide the most supportive evidence for BNN-dealksylation being catalyzed by CYP 3A4.

Involvement of cytochrome P450 3A4 in N-dealkylation of buprenorphine in human liver microsomes.

Inhibition by fluoxetine of cytochrome P450 2D6 activity

Inhibition of CYP2D6 activity in patients undergoing treatment with fluoxetine or other serotonin uptake inhibitors could contribute to toxicity or attenuated response from concurrent medications that are substrates of this enzyme.

Designer Drugs That Are Potent Inhibitors of CYP2D6

Conurrent oral use of CYP2D6 substrates with MPPP and PEPAP may represent a kinetic drug interaction risk, but this risk must be confirmed clinically.

Assessment of specificity of eight chemical inhibitors using cDNA-expressed cytochromes P450

  • Y. SaiR. Dai M. Shou
  • Biology, Chemistry
    Xenobiotica; the fate of foreign compounds in biological systems
  • 2000
The results indicate that sulphaphenazole, quinidine and α-naphthoflavone are selective inhibitors of CYP2C9, CyP2D6 and CYP1A isoforms on the basis of the IC50, which are much lower than those of other P450 isoforms (> 10-fold).

Differential selectivity of cytochrome P450 inhibitors against probe substrates in human and rat liver microsomes.

It is evident that CYP inhibitors do not exhibit the same selectivity in human and rat liver microsomes, due to differential selectivity of the inhibitors and/or differences in the CYP isoform responsible for metabolism in the different species.

Orphenadrine and methimazole inhibit multiple cytochrome P450 enzymes in human liver microsomes.

This study indicates orphenadrine cannot be used as a selective inhibitor of CYP2B6 in human liver microsomes and that methimazole is not a selective inhibitors of the flavin-containing monooxygenase in human Liver P450 enzyme activities.

Cytochrome P450 isoform inhibitors as a tool for the investigation of metabolic reactions catalyzed by human liver microsomes.

Investigation of human liver microsomes for cytochrome P450 isoform-dependent reactions found alpha-Naphthoflavone and furafylline both inhibited phenacetin and 7-ethoxyresorufin O-deethylation processes, a consequence of the absence of CYP1A1 in noninduced human liver.