title: Metabolic capabilities of cytochrome P450 enzymes in Chinese liver microsomes compared with those in Caucasian liver microsomes.
abstract: OBJECTIVE
  The most common causes of variability in drug response include differences in drug metabolism, especially when the hepatic cytochrome P450 (CYP) enzymes are involved. The current study was conducted to assess the differences in CYP activities in human liver microsomes (HLM) of Chinese or Caucasian origin.
  
  
  METHODS
  The metabolic capabilities of CYP enzymes in 30 Chinese liver microsomal samples were compared with those of 30 Caucasian samples utilizing enzyme kinetics. Phenacetin O-deethylation, coumarin 7-hydroxylation, bupropion hydroxylation, amodiaquine N-desethylation, diclofenac 4'-hydroxylation (S)-mephenytoin 4'-hydroxylation, dextromethorphan O-demethylation, chlorzoxazone 6-hydroxylation and midazolam 1'-hydroxylation/testosterone 6β-hydroxylation were used as probes for activities of CYP1A2, CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP2E1 and CYP3A, respectively. Mann-Whitney U test was used to assess the differences.
  
  
  RESULTS
  The samples of the two ethnic groups were not significantly different in cytochrome-b(5) concentrations but were significantly different in total CYP concentrations and NADPH-P450 reductase activity (P < 0.05). Significant ethnic differences in intrinsic clearance were observed for CYP1A2, CYP2C9, CYP2C19 and CYP2E1; the median values of the Chinese group were 54, 58, 26, and 35% of the corresponding values of the Caucasian group, respectively. These differences were associated with differences in Michaelis constant or maximum velocity. Despite negligible difference in intrinsic clearance, the Michaelis constant of CYP2B6 appeared to have a significant ethnic difference. No ethnic difference was observed for CYP2A6, CYP2C8, CYP2D6 and CYP3A.
  
  
  CONCLUSIONS
  These data extend our knowledge on the ethnic differences in CYP enzymes and will have implications for drug discovery and drug therapy for patients from different ethnic origins.
authors.affiliation: Shanghai Institute of Materia, Chinese Academy of Sciences, Shanghai, China.
authors.forename: Junling
authors.initials: J
authors.lastname: Yang
authors.forename: Minxia M
authors.initials: MM
authors.lastname: He
authors.forename: Wei
authors.initials: W
authors.lastname: Niu
authors.forename: Steven A
authors.initials: SA
authors.lastname: Wrighton
authors.forename: Li
authors.initials: L
authors.lastname: Li
authors.forename: Yang
authors.initials: Y
authors.lastname: Liu
authors.forename: Chuan
authors.initials: C
authors.lastname: Li
mesh_terms: D000328:Adult; D000368:Aged; D044466:Asian People; D002853:Chromatography, Liquid; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D015786:Cytochromes b5 / Q000378:metabolism; D005260:Female; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism; D008297:Male; D008862:Microsomes, Liver / Q000201:enzymology*; D008875:Middle Aged; D009251:NADPH-Ferrihemoprotein Reductase / Q000378:metabolism; D012044:Regression Analysis; D053719:Tandem Mass Spectrometry; D044465:White People; D055815:Young Adult
chemical_list: D007527:Isoenzymes; D015786:Cytochromes b5; D003577:Cytochrome P-450 Enzyme System; D009251:NADPH-Ferrihemoprotein Reductase