AI Article Synopsis
- The study investigated how different CYP2C9 genetic variants affect the metabolism of propofol, a common anesthetic, using in vitro experiments with engineered insect cells.
- Some variants of CYP2C9 displayed reduced enzymatic activity compared to the wild type, while two specific variants (*36 and *56) showed enhanced metabolic clearance of propofol.
- This research provides new insights into rare CYP2C9 alleles and lays the groundwork for future clinical studies on their role in propofol metabolism in patients.
Article 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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| http://dx.doi.org/10.1248/bpb.b14-00671 | DOI Listing |
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