Impact of CYP2C9 Polymorphism Found in the Chinese Population on the Metabolism of Propofol <i>in Vitro</i>

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  • Lian Qing-Quan
    Department of Anesthesiology, The Second Affiliated Hospital of Wenzhou Medical University
  • Pan Pei-Pei
    School of Pharmacy, Wenzhou Medical University
  • Li Jun-Wei
    School of Pharmacy, Wenzhou Medical University
  • Lin Han
    Department of Anesthesiology, The Second Affiliated Hospital of Wenzhou Medical University
  • Hu Guo-Xin
    School of Pharmacy, Wenzhou Medical University
  • Zuo Ming-Zhang
    Department of Anesthesia, Beijing Hospital, Ministry of Health
  • Cai Jian-Ping
    The Key Laboratory of Geriatrics, Beijing Hospital and Beijing Institute of Geriatrics, Ministry of Health

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  • Impact of CYP2C9 Polymorphism Found in the Chinese Population on the Metabolism of Propofol in Vitro

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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.

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