Hemodialysis does not alter in vitro hepatic CYP3A4 and CYP2D6 metabolic activity in uremic serum

Brian S Decker,1,2 Kalisha D O'Neill,1,2 Mary A Chambers,1,2 James E Slaven,3 Zhangsheng Yu,3 David R Jones,2,4 Sharon M Moe1,21Division of Nephrology, 2Department of Medicine, 3Department of Biostatistics, 4Division of Clinical Pharmacology, Department of Medicine, School of Medicine, Indi...

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Autores principales: Decker BS, O’Neill KD, Chambers MA, Slaven JE, Yu Z, Jones DR, Moe SM
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Lenguaje:EN
Publicado: Dove Medical Press 2013
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spelling oai:doaj.org-article:d82cb1c678b2461bbfce3d17f96abe1d2021-12-02T00:22:26ZHemodialysis does not alter in vitro hepatic CYP3A4 and CYP2D6 metabolic activity in uremic serum1179-1438https://doaj.org/article/d82cb1c678b2461bbfce3d17f96abe1d2013-12-01T00:00:00Zhttp://www.dovepress.com/hemodialysis-does-not-alter-in-vitro-hepatic-cyp3a4-and-cyp2d6-metabol-a15250https://doaj.org/toc/1179-1438 Brian S Decker,1,2 Kalisha D O'Neill,1,2 Mary A Chambers,1,2 James E Slaven,3 Zhangsheng Yu,3 David R Jones,2,4 Sharon M Moe1,21Division of Nephrology, 2Department of Medicine, 3Department of Biostatistics, 4Division of Clinical Pharmacology, Department of Medicine, School of Medicine, Indiana University, Indianapolis, IN, USAAbstract: 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.Keywords: hemodialysis, uremia, CYP3A4, CYP2D6, metabolismDecker BSO’Neill KDChambers MASlaven JEYu ZJones DRMoe SMDove Medical PressarticleTherapeutics. PharmacologyRM1-950ENClinical Pharmacology: Advances and Applications, Vol 2013, Iss Issue 1, Pp 193-199 (2013)
institution DOAJ
collection DOAJ
language EN
topic Therapeutics. Pharmacology
RM1-950
spellingShingle Therapeutics. Pharmacology
RM1-950
Decker BS
O’Neill KD
Chambers MA
Slaven JE
Yu Z
Jones DR
Moe SM
Hemodialysis does not alter in vitro hepatic CYP3A4 and CYP2D6 metabolic activity in uremic serum
description Brian S Decker,1,2 Kalisha D O'Neill,1,2 Mary A Chambers,1,2 James E Slaven,3 Zhangsheng Yu,3 David R Jones,2,4 Sharon M Moe1,21Division of Nephrology, 2Department of Medicine, 3Department of Biostatistics, 4Division of Clinical Pharmacology, Department of Medicine, School of Medicine, Indiana University, Indianapolis, IN, USAAbstract: 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.Keywords: hemodialysis, uremia, CYP3A4, CYP2D6, metabolism
format article
author Decker BS
O’Neill KD
Chambers MA
Slaven JE
Yu Z
Jones DR
Moe SM
author_facet Decker BS
O’Neill KD
Chambers MA
Slaven JE
Yu Z
Jones DR
Moe SM
author_sort Decker BS
title Hemodialysis does not alter in vitro hepatic CYP3A4 and CYP2D6 metabolic activity in uremic serum
title_short Hemodialysis does not alter in vitro hepatic CYP3A4 and CYP2D6 metabolic activity in uremic serum
title_full Hemodialysis does not alter in vitro hepatic CYP3A4 and CYP2D6 metabolic activity in uremic serum
title_fullStr Hemodialysis does not alter in vitro hepatic CYP3A4 and CYP2D6 metabolic activity in uremic serum
title_full_unstemmed Hemodialysis does not alter in vitro hepatic CYP3A4 and CYP2D6 metabolic activity in uremic serum
title_sort hemodialysis does not alter in vitro hepatic cyp3a4 and cyp2d6 metabolic activity in uremic serum
publisher Dove Medical Press
publishDate 2013
url https://doaj.org/article/d82cb1c678b2461bbfce3d17f96abe1d
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