Decker Brian S, O'Neill Kalisha D, Chambers Mary A, Slaven James E, Yu Zhangsheng, Jones David R, Moe Sharon M
Division of Nephrology, Department of Medicine, School of Medicine, Indiana University, Indianapolis, IN, USA ; Department of Medicine, Department of Medicine, School of Medicine, Indiana University, Indianapolis, IN, USA.
Department of Biostatistics, Department of Medicine, School of Medicine, Indiana University, Indianapolis, IN, USA.
Clin Pharmacol. 2013 Dec 10;5:193-9. doi: 10.2147/CPAA.S54381. eCollection 2013.
There is a paucity of studies evaluating the change in liver metabolism in subjects receiving hemodialysis. The purpose of this study was to compare the effect of uremic toxins on hepatic cytochrome P450 (CYP)3A4 and CYP2D6 metabolism before and after a 4-hour hemodialysis session. Midazolam and dextromethorphan were incubated with uremic serum collected from subjects before and after the 4-hour hemodialysis session. Analysis and quantification of the 1'-OH-midazolam and 4-OH-midazolam and dextrorphan metabolites were performed by high-pressure liquid chromatography/mass spectrometry. Statistical analysis using the Student's t-test (paired) was used to compare the amount of metabolite formed. The mean amount of 1'-OH-midazolam, 4-OH-midazolam, and dextrorphan metabolites formed before and after hemodialysis did not significantly differ. There was no significant difference in CYP3A4 and CYP2D6 metabolic activity in uremic serum before and after hemodialysis.
评估接受血液透析的受试者肝脏代谢变化的研究较少。本研究的目的是比较尿毒症毒素对4小时血液透析疗程前后肝细胞色素P450(CYP)3A4和CYP2D6代谢的影响。将咪达唑仑和右美沙芬与4小时血液透析疗程前后从受试者采集的尿毒症血清一起孵育。通过高压液相色谱/质谱法对1'-羟基咪达唑仑、4-羟基咪达唑仑和右啡烷代谢物进行分析和定量。使用配对学生t检验进行统计分析,以比较形成的代谢物量。血液透析前后形成的1'-羟基咪达唑仑、4-羟基咪达唑仑和右啡烷代谢物的平均量没有显著差异。血液透析前后尿毒症血清中CYP3A4和CYP2D6的代谢活性没有显著差异。