In vivo induction of CYP in mice by carbamazepine is independent on PXR.

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Liu A, Wang C, Hehir M, Zhou T, Yang J

In vivo induction of CYP in mice by carbamazepine is independent on PXR.

Pharmacol Rep. 2015 Apr;67(2):299-304. doi: 10.1016/j.pharep.2014.10.002. Epub 2014 Oct 18.

PubMed ID

25712654 [ View in PubMed

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Abstract

BACKGROUND: The antiepileptic drug carbamazepine (CBZ) is a typical inducer of cytochrome P450 (CYP) 3A and 2C in the clinic. It is considered a strong constitutive androstane receptor activator, however both CBZ and its main metabolite CBZ 10, 11-epoxide have been reported to be pregnane X receptor (PXR) activators whose maximal efficacy and potency are comparable with the human PXR ligand rifampicin. It is unknown whether or not PXR plays a substantially important role in in vivo induction of CYP by CBZ administration. METHODS: In this study, wild type and Pxr-/- mice were administered with CBZ for 5 days. Serum and liver samples were collected and subjected to hepatotoxicity assessment and CYP induction analysis. RESULTS: CYP2b, 2c and 3a were induced similarly in terms of transcription level, enzyme activity and protein abundance in both wild type and Pxr-/- mice. Inductive profile of CYPs in mice by CBZ administration accorded with those reported in rats, but differed from clinically reported data. CONCLUSIONS: These data suggest that in vivo induction of CYP in mice by multiple administration of CBZ is independent of PXR. Knowledge of the featured CYP induction profile in mice helps us understand species related CYP induction profiles among rodents and humans resulting from administration of CBZ.

DrugBank Data that Cites this Article

Drug Enzymes

Drug	Enzyme	Kind	Organism	Pharmacological Action	Actions
Carbamazepine	Cytochrome P450 2C8	Protein	Humans	Unknown	Substrate Inducer	Details