Lian Qing-Quan, Pan Pei-Pei, Li Jun-Wei, Lin Han, Hu Guo-Xin, Zuo Ming-Zhang, Cai Jian-Ping
Department of Anesthesiology, The Second Affiliated Hospital of Wenzhou Medical University.
Biol Pharm Bull. 2015;38(4):531-5. doi: 10.1248/bpb.b14-00671.
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 CYP2C91 and other variants. Some of the variants showed decreased enzyme activity compared with the wild type, as previously reported. Two variants (CYP2C936 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.
在体外研究了参与广泛使用的麻醉剂丙泊酚生物转化的微粒体CYP2C9等位基因。为了检测CYP2C9等位基因的酶活性，在携带CYP2C91和其他变体的Sf21昆虫细胞的重组人P450 CYP2C9微粒体中测定了丙泊酚4-羟化的动力学参数。如先前报道，一些变体与野生型相比酶活性降低。发现两个变体（CYP2C936和56）相对于野生型变体显著增加内在清除率。除11、47和54外，大多数变体与野生型相比显著（p<0.05）降低了丙泊酚的内在清除率。本研究首次报道了这些丙泊酚代谢的罕见等位基因，为进一步在体内研究CYP2C9等位基因对丙泊酚代谢的临床研究提供了基础数据。
