title: In vivo induction of CYP in mice by carbamazepine is independent on PXR.
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.
authors.affiliation: Medical School of Ningbo University, Ningbo, China.
authors.forename: Aiming
authors.initials: A
authors.lastname: Liu
authors.affiliation: Medical School of Ningbo University, Ningbo, China.
authors.forename: Chuang
authors.initials: C
authors.lastname: Wang
authors.affiliation: Medical School of Ningbo University, Ningbo, China.
authors.forename: Michael
authors.initials: M
authors.lastname: Hehir
authors.affiliation: Hepatobiliary Surgery Centre, Ningbo No. 2 Hospital, Ningbo, China. Electronic address: zhoutb68@126.com.
authors.forename: Tianbao
authors.initials: T
authors.lastname: Zhou
authors.affiliation: Ningbo College of Health Sciences, Ningbo, China. Electronic address: yangjl@nchs.edu.cn.
authors.forename: Julin
authors.initials: J
authors.lastname: Yang
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases / Q000096:biosynthesis*; D001219:Aspartate Aminotransferases / Q000097:blood; D002220:Carbamazepine / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology*; D051544:Cytochrome P-450 CYP3A / Q000096:biosynthesis*; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis* / Q000378:metabolism*; D000072467:Cytochrome P450 Family 2; D004790:Enzyme Induction / Q000187:drug effects; D008099:Liver / Q000187:drug effects* / Q000201:enzymology; D008297:Male; D008565:Membrane Proteins / Q000096:biosynthesis*; D051379:Mice; D018345:Mice, Knockout; D000077297:Pregnane X Receptor; D011987:Receptors, Steroid / Q000172:deficiency* / Q000235:genetics; D013250:Steroid Hydroxylases / Q000096:biosynthesis*
chemical_list: D008565:Membrane Proteins; D000077297:Pregnane X Receptor; D011987:Receptors, Steroid; D002220:Carbamazepine; D003577:Cytochrome P-450 Enzyme System; C000610388:cytochrome P-450 2C37, mouse; D013250:Steroid Hydroxylases; D001189:Aryl Hydrocarbon Hydroxylases; C121503:Cyp2b9 protein, mouse; C086292:Cyp2c29 protein, mouse; C496508:Cyp3a11 protein, mouse; D051544:Cytochrome P-450 CYP3A; D000072467:Cytochrome P450 Family 2; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase
keywords: CYP; Carbamazepine; Independent; Induction; PXR