title: Impact of CYP2C9 polymorphism found in the Chinese population on the metabolism of propofol in vitro.
abstract: The microsomal CYP2C9 alleles involved in the biotransformation of propofol, a widely used anesthetic agent, were investigated in vitro. To examine the enzymatic activity of the CYP2C9 alleles, kinetic parameters for propofol 4-hydroxylation were determined in recombinant human P450s CYP2C9 microsomes from Sf21 insects cells carrying CYP2C9*1 and other variants. Some of the variants showed decreased enzyme activity compared with the wild type, as previously reported. Two variants (CYP2C9*36 and *56) were found substantially to increase intrinsic clearance relative to the wild type variant. Most variants significantly (p<0.05) decreased intrinsic clearance of propofol compared with the wild type, except *11, *47, and *54. This study is the first to report these rare alleles for propofol metabolism, providing fundamental data for further clinical studies on CYP2C9 alleles for propofol metabolism in vivo.
authors.affiliation: Department of Anesthesiology, The Second Affiliated Hospital of Wenzhou Medical University.
authors.forename: Qing-Quan
authors.initials: QQ
authors.lastname: Lian
authors.forename: Pei-Pei
authors.initials: PP
authors.lastname: Pan
authors.forename: Jun-Wei
authors.initials: JW
authors.lastname: Li
authors.forename: Han
authors.initials: H
authors.lastname: Lin
authors.forename: Guo-Xin
authors.initials: GX
authors.lastname: Hu
authors.forename: Ming-Zhang
authors.initials: MZ
authors.lastname: Zuo
authors.forename: Jian-Ping
authors.initials: JP
authors.lastname: Cai
mesh_terms: D000483:Alleles; D000777:Anesthetics / Q000378:metabolism*; D000818:Animals; D044466:Asian People / Q000235:genetics; D002460:Cell Line; D065729:Cytochrome P-450 CYP2C9 / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D006900:Hydroxylation; D007313:Insecta; D008861:Microsomes / Q000378:metabolism; D009154:Mutation; D011110:Polymorphism, Genetic; D015742:Propofol / Q000378:metabolism*
chemical_list: D000777:Anesthetics; C450260:CYP2C9 protein, human; D065729:Cytochrome P-450 CYP2C9; D015742:Propofol