Induction of Xenobiotic Receptors, Transporters, and Drug Metabolizing Enzymes by Oxycodone

Hassan, Hazem E.; Myers, Alan L.; Lee, Insong J.; Mason, Charles E.; Sinz, Michael; Wang, Hongbing; Eddington, Natalie D.

doi:10.1124/dmd.112.050401

Cited by 7 publications

(2 citation statements)

References 59 publications

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“…One possible explanation of the morphine toleranceinduced ketamine accumulation would be the downregulation of a ketamine (or its metabolite) efflux transporter or the up-regulation of a reuptake transporter. The effects of chronic morphine treatment on the induction of xenobiotic receptors, transporters and drug-metabolizing enzymes is not thoroughly known, but chronic oxycodone has been reported to significantly down-or up-regulate 27 different drug transporters in the rat liver (Hassan et al, 2013).…”

Section: Effects Of Chronic Morphine Treatment On Ketamine and Norketmentioning

confidence: 99%

Ketamine coadministration attenuates morphine tolerance and leads to increased brain concentrations of both drugs in the rat

Lilius

Jokinen

Neuvonen

et al. 2015

British J Pharmacology

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Background and PurposeThe effects of ketamine in attenuating morphine tolerance have been suggested to result from a pharmacodynamic interaction. We studied whether ketamine might increase brain morphine concentrations in acute coadministration, in morphine tolerance and morphine withdrawal.Experimental ApproachMorphine minipumps (6 mg·day–1) induced tolerance during 5 days in Sprague–Dawley rats, after which s.c. ketamine (10 mg·kg–1) was administered. Tail flick, hot plate and rotarod tests were used for behavioural testing. Serum levels and whole tissue brain and liver concentrations of morphine, morphine-3-glucuronide, ketamine and norketamine were measured using HPLC-tandem mass spectrometry.Key ResultsIn morphine-naïve rats, ketamine caused no antinociception whereas in morphine-tolerant rats there was significant antinociception (57% maximum possible effect in the tail flick test 90 min after administration) lasting up to 150 min. In the brain of morphine-tolerant ketamine-treated rats, the morphine, ketamine and norketamine concentrations were 2.1-, 1.4- and 3.4-fold, respectively, compared with the rats treated with morphine or ketamine only. In the liver of morphine-tolerant ketamine-treated rats, ketamine concentration was sixfold compared with morphine-naïve rats. After a 2 day morphine withdrawal period, smaller but parallel concentration changes were observed. In acute coadministration, ketamine increased the brain morphine concentration by 20%, but no increase in ketamine concentrations or increased antinociception was observed.Conclusions and ImplicationsThe ability of ketamine to induce antinociception in rats made tolerant to morphine may also be due to increased brain concentrations of morphine, ketamine and norketamine. The relevance of these findings needs to be assessed in humans.

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Section: Effects Of Chronic Morphine Treatment On Ketamine and Norketmentioning

confidence: 99%

Ketamine coadministration attenuates morphine tolerance and leads to increased brain concentrations of both drugs in the rat

Lilius

Jokinen

Neuvonen

et al. 2015

British J Pharmacology

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“…In cultured rat hepatocytes, arsenite decreases induction of CYP1A1 and 1A2 by TCDD via a mechanism involving decreased AHR nuclear accumulation, increased binding of cytosolic AHR to chaperones, and induction of heme oxygenase-1 (Anwar-Mohamed et al, 2012). In vivo treatment of rats with oxycodone increases hepatic AHR mRNA levels, but oxycodone and its major metabolites (noroxycodone and oxymorphone) are not direct AHR activators (Hassan et al, 2013).…”

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confidence: 95%

Fifty Years of Aryl Hydrocarbon Receptor Research as Reflected in the Pages ofDrug Metabolism and Disposition

Riddick

2023

Drug Metab Dispos

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The induction of multiple drug-metabolizing enzymes by halogenated and polycyclic aromatic hydrocarbon toxicants is mediated by the aryl hydrocarbons receptor (AHR). This fascinating receptor also has natural dietary and endogenous ligands, and much is now appreciated about the AHR's developmental and physiological roles, as well as its importance in cancer and other diseases. The past several years has witnessed increasing emphasis on understanding the multifaceted roles of the AHR in the immune system. Most would agree that the "discovery" of the AHR occurred in 1976, with the report of specific binding of a high affinity radioligand in mouse liver, just three years after the launch of the journal Drug Metabolism and Disposition (DMD) in 1973. Over the ensuing fifty years, the AHR and DMD have led parallel and often intersecting lives. The overall goal of this minireview is to provide a decade-by-decade overview of major historical landmark discoveries in the AHR field and to highlight the numerous contributions made by publications appearing in the pages of DMD. It is hoped that this historical tour might inspire current and future research in the AHR field. Significance Statement With the launch of Drug Metabolism and Disposition (DMD) in 1973 and the discovery of the aryl hydrocarbon receptor (AHR) in 1976, the journal and the receptor have led parallel and often intersecting lives over the past fifty years. Tracing the history of the AHR can reveal how knowledge in the field has evolved to the present and highlight the important contributions made by discoveries reported in DMD. This may inspire additional DMD papers reporting future AHR landmark discoveries.

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Genomics and Drug Transporters and Application in Drug Discovery, Delivery, and Development

Gharavi

Hassan

2018

Genomics-Driven Healthcare

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Induction of Xenobiotic Receptors, Transporters, and Drug Metabolizing Enzymes by Oxycodone

Cited by 7 publications

References 59 publications

Ketamine coadministration attenuates morphine tolerance and leads to increased brain concentrations of both drugs in the rat

Ketamine coadministration attenuates morphine tolerance and leads to increased brain concentrations of both drugs in the rat

Fifty Years of Aryl Hydrocarbon Receptor Research as Reflected in the Pages ofDrug Metabolism and Disposition

Genomics and Drug Transporters and Application in Drug Discovery, Delivery, and Development

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