title: Effect of codeine on CYP450 isoform activity of rats.
abstract: BACKGROUND
  Codeine, also known as 3-methylmorphine, is an opiate used to treat pain, as a cough medicine and for diarrhoea. No study on the effects of codeine on the metabolic capacity of CYP enzyme is reported.
  
  
  OBJECTIVE
  In order to investigate the effects of codeine on the metabolic capacity of cytochrome P450 (CYP) enzymes, a cocktail method was employed to evaluate the activities of CYP2B1, CYP2D1, CYP1A2, CYP3A2 and CYP2C11.
  
  
  METHODS
  Sprague-Dawley rats were randomly divided into codeine group (low, medium, high) and control group. The codeine group rats were given 4, 8, 16 mg/kg (low, medium, high) codeine by continuous intragastric administration for 14 days. Five probe drugs bupropion, metroprolol, phenacetin, midazolam and tolbutamide were given to rats through intragastric administration, and the plasma concentrations were determined by UPLC-MS/MS.
  
  
  CONCLUSIONS
  The pharmacokinetic parameters of bupropion and metroprolol experienced obvious change with AUC(0-t), Cmaxincreased and CL decreased for bupropion in medium dosage group and midazolam low dosage group. This result indicates that the 14 day-intragastric administration of codeine may inhibit the metabolism of bupropion (CYP2B1) and midazolam (CYP3A2) in rat. Additional, there are no statistical differences for albumin (ALB), alkaline phosphatase (ALP), creatinine (Cr) after 14 intragastric administration of codeine, while alanine aminotransferase (ALT), aspartate aminotransferase (AST), uric acid (UA) increased compared to control group. The biomedical test results show continuous 14 day-intragastric administration of codeine would cause liver damage.
authors.affiliation: a The Laboratory of Clinical Pharmacy , The People's Hospital of Lishui , Lishui , China.
authors.forename: Shuanghu
authors.initials: S
authors.lastname: Wang
authors.affiliation: b Laboratory Animal Centre of Wenzhou Medical University , Wenzhou , China.
authors.forename: Yanwen
authors.initials: Y
authors.lastname: Dong
authors.affiliation: b Laboratory Animal Centre of Wenzhou Medical University , Wenzhou , China.
authors.forename: Ke
authors.initials: K
authors.lastname: Su
authors.affiliation: b Laboratory Animal Centre of Wenzhou Medical University , Wenzhou , China.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhang
authors.affiliation: b Laboratory Animal Centre of Wenzhou Medical University , Wenzhou , China.
authors.forename: Linyi
authors.initials: L
authors.lastname: Wang
authors.affiliation: b Laboratory Animal Centre of Wenzhou Medical University , Wenzhou , China.
authors.forename: Anyue
authors.initials: A
authors.lastname: Han
authors.affiliation: b Laboratory Animal Centre of Wenzhou Medical University , Wenzhou , China.
authors.forename: Congcong
authors.initials: C
authors.lastname: Wen
authors.affiliation: c Analytical and Testing Center of Wenzhou Medical University , Wenzhou , China.
authors.forename: Xianqin
authors.initials: X
authors.lastname: Wang
authors.affiliation: d The Institute of Molecular Medicine, School of Optometry and Ophthalmology and Eye Hospital, Wenzhou Medical University , Wenzhou , China.
authors.forename: Yan
authors.initials: Y
authors.lastname: He
mesh_terms: D000818:Animals; D016642:Bupropion / Q000378:metabolism; D003061:Codeine / Q000378:metabolism* / Q000494:pharmacology*; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions / Q000502:physiology; D004789:Enzyme Activation / Q000187:drug effects / Q000502:physiology; D007527:Isoenzymes / Q000378:metabolism; D008297:Male; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D014044:Tolbutamide / Q000378:metabolism
chemical_list: D007527:Isoenzymes; D016642:Bupropion; D003577:Cytochrome P-450 Enzyme System; D014044:Tolbutamide; D003061:Codeine
keywords: Cocktail; UPLC-MS/MS; biochemical; bupropion; midazolam