In Vivo Activity of Norhydrocodone: An Active Metabolite of Hydrocodone

@article{Navani2013InVA,
  title={In Vivo Activity of Norhydrocodone: An Active Metabolite of Hydrocodone},
  author={Dipesh M. Navani and Byron C. Yoburn},
  journal={The Journal of Pharmacology and Experimental Therapeutics},
  year={2013},
  volume={347},
  pages={497 - 505}
}
  • Dipesh M. NavaniB. Yoburn
  • Published 1 November 2013
  • Biology, Medicine
  • The Journal of Pharmacology and Experimental Therapeutics
Hydrocodone is primarily metabolized to hydromorphone and norhydrocodone. Although hydromorphone is a known active metabolite of hydrocodone, the in vivo activity of norhydrocodone is not well documented. In the current study, the pharmacodynamics of norhydrocodone were evaluated and compared with hydrocodone and hydromorphone. Binding studies established that norhydrocodone, similar to hydrocodone and hydromorphone, is a μ-selective opioid ligand. In vivo analgesia studies (tail flick… 

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References

SHOWING 1-10 OF 36 REFERENCES

Excretion profile of hydrocodone, hydromorphone and norhydrocodone in urine following single dose administration of hydrocodone to healthy volunteers.

Although hydromorphone was found at lower levels than hydrocodone, in six of seven subjects, it persisted for as long as hydrocdone was detected, thus making the nor-metabolite a valuable tool in evaluating hydrocidone use and/or misuse.

Effect of cytochrome P450 2D1 inhibition on hydrocodone metabolism and its behavioral consequences in rats.

Data suggest that differences in CYP2D6 phenotype will have limited influence on the drug response to hydrocodone after nonoral administration, verified in a study showing that inhibition of hydrocODone biotransformation to hydromorphone does not affect measures of abuse liability.

Inhibition of cytochrome P450 2D6 metabolism of hydrocodone to hydromorphone does not importantly affect abuse liability.

The data suggest only a small role of hydromorphone in eliciting abuse-related responses to oral hydrocodone, and quinidine had no consistent effect on their responses, even thoughQuinidine abolished the pre-existing metabolic differences in hydrom orphone production, as measured in urine.

Effect of Cytochrome P 450 2 D 1 Inhibition on Hydrocodone Metabolism and its Behavioral Consequences in Rats 1

Data suggest that differences in CYP2D6 phenotype will have limited influence on the drug response to hydrocodone after nonoral administration, and this has recently been verified in a study showing that inhibition of hydrocODone biotransformation to hydromorphone does not affect measures of abuse liability.

CYP2D6 phenotype determines the metabolic conversion of hydrocodone to hydromorphone

The data establish the importance of CYP2D6 in the formation of hydromorphone from hydrocodone and suggest that the activity of this enzyme may limit the abuse liability of hydrocODone.

Response to hydrocodone, codeine and oxycodone in a CYP2D6 poor metabolizer

Activation of G-Proteins by Morphine and Codeine Congeners: Insights to the Relevance of O- and N-Demethylated Metabolites at μ- and δ-Opioid Receptors

7,8-saturated codeine congeners are more efficacious than codeine, which may explain their lack of requirement for 3-O-demethylation in vivo, and further research is needed to understand the relationship between metabolism and in vivo activity of these compounds.

CYP2D6 and CYP3A4 involvement in the primary oxidative metabolism of hydrocodone by human liver microsomes.

The O-demethylation of hydrocodone is predominantly catalyzed by CYP2D6 and to a lesser extent by an unknown low affinity cytochrome p450 enzyme, and the genetic polymorphisms of CYP 2D6 may influence hydromorphone metabolism and its therapeutic efficacy.