Metabolism of deltamethrin and cis- and trans-permethrin by human expressed cytochrome P450 and carboxylesterase enzymes

被引：19

作者：

Hedges, Laura ^{[1
]}

Brown, Susan ^{[1
]}

MacLeod, A. Kenneth ^{[1
]}

Vardy, Audrey ^{[1
]}

Doyle, Edward ^{[1
]}

Song, Gina ^{[2
]}

Moreau, Marjory ^{[2
]}

Yoon, Miyoung ^{[3
]}

Osimitz, Thomas G. ^{[4
]}

Lake, Brian G. ^{[1
,5
]}

机构：

[1] Concept Life Sci, CXR Biosci Ltd, Dundee, Scotland

[2] ScitoVation LLC, Res Triangle Pk, NC USA

[3] ToxStrategies LLC, Res Triangle Pk, NC USA

[4] Sci Strategies LLC, Charlottesville, VA USA

[5] Univ Surrey, Ctr Toxicol, Guildford, Surrey, England

来源：

XENOBIOTICA | 2019年 / 49卷 / 05期

关键词：

Carboxylesterase; cis-permethrin; cytochrome P450; deltamethrin; human; liver microsomes; liver cytosol; trans-permethrin; IN-VIVO PHARMACOKINETICS; HUMAN LIVER; HYDROLYTIC METABOLISM; VITRO METABOLISM; RAT; PYRETHROIDS; EXTRAPOLATION; NEUROTOXICITY; MECHANISMS; TOXICOLOGY;

D O I：

10.1080/00498254.2018.1474283

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

The metabolism of the pyrethroids deltamethrin (DLM), cis-permethrin (CPM) and trans-permethrin (TPM) was studied in human expressed cytochrome P450 (CYP) and carboxylesterase (CES) enzymes. DLM, CPM and TPM were metabolised by human CYP2B6 and CYP2C19, with the highest apparent intrinsic clearance (CLint) values for pyrethroid metabolism being observed with CYP2C19. Other CYP enzymes contributing to the metabolism of one or more of the three pyrethroids were CYP1A2, CYP2C8, CYP2C9*1, CYP2D6*1, CYP3A4 and CYP3A5. None of the pyrethroids were metabolised by CYP2A6, CYP2E1, CYP3A7 or CYP4A11. DLM, CPM and TPM were metabolised by both human CES1 and CES2 enzymes. Apparent CLint values for pyrethroid metabolism by CYP and CES enzymes were scaled to per gram of adult human liver using abundance values for microsomal CYP enzymes and for CES enzymes in liver microsomes and cytosol. TPM had the highest and CPM the lowest apparent CLint values for total metabolism (CYP and CES enzymes) per gram of adult human liver. Due to their higher abundance, all three pyrethroids were extensively metabolised by CES enzymes in adult human liver, with CYP enzymes only accounting for 2%, 10% and 1% of total metabolism for DLM, CPM and TPM, respectively.

引用

页码：521 / 527

页数：7

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