Comparative metabolism of mycophenolic acid by glucuronic acid and glucose conjugation in human, dog, and cat liver microsomes.
Comparative metabolism of mycophenolic acid by glucuronic acid and glucose conjugation in human, dog, and cat liver microsomes.
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DOI：
10.1111/jvp.12338
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发表时间：
2017-04
影响因子：
1.3
通讯作者：
Court MH
中科院分区：
文献类型：
--
作者：
Slovak JE;Mealey K;Court MH
在猫中使用免疫抑制剂麦考酚酸（MPA）是有限的，因为MPA消除取决于葡萄糖醛酸化，这是缺乏猫。我们使用16只猫、26只狗和48个人的肝微粒体评价了主要（苯酚葡萄糖醛酸苷）和次要（酰基葡萄糖醛酸苷、苯酚葡萄糖苷和酰基葡萄糖苷）MPA代谢物的形成。所有MPA代谢产物均由人肝微粒体形成，而犬和猫肝微粒体形成两种MPA葡糖苷酸，但仅形成一种MPA葡萄糖苷（苯酚葡萄糖苷）。猫肝微粒体中MPA对苯酚葡萄糖醛酸化的固有清除率（克林特）仅为犬和人肝微粒体的15-17%。然而，猫肝微粒体中酰基葡糖苷酸和苯酚葡糖苷形成的克林特与犬和人肝微粒体中的CLint相似或更大。虽然猫肝微粒体的总MPA结合克林特与犬和人肝微粒体相似，但种属间各途径的相对贡献不同，犬和人肝微粒体中以苯酚葡萄糖醛酸化为主，猫肝微粒体中以苯酚糖苷化为主。猫肝微粒体之间的MPA结合变化为3倍，总结合和苯酚葡萄糖苷化，6倍，苯酚葡萄糖醛酸化和11倍，酰基葡萄糖醛酸化。我们的研究结果表明，总MPA共轭是定量相似的肝微粒体从猫，狗，和人类，尽管大的差异，这些物种所利用的共轭途径。
Use of the immunosuppressant mycophenolic acid (MPA) in cats is limited because MPA elimination depends on glucuronidation, which is deficient in cats. We evaluated formation of major (phenol glucuronide) and minor (acyl glucuronide, phenol glucoside, and acyl glucoside) MPA metabolites using liver microsomes from 16 cats, 26 dogs, and 48 humans. All MPA metabolites were formed by human liver microsomes, while dog and cat liver microsomes formed both MPA glucuronides, but only one MPA glucoside (phenol glucoside). Intrinsic clearance (CLint) of MPA for phenol glucuronidation by cat liver microsomes was only 15–17% that of dog and human liver microsomes. However CLint for acyl glucuronide and phenol glucoside formation in cat liver microsomes was similar to or greater than that for dog and human liver microsomes. While total MPA conjugation CLint was generally similar for cat liver microsomes compared with dog and human liver microsomes, relative contributions of each pathway varied between species with phenol glucuronidation predominating in dog and human liver microsomes and phenol glucosidation predominating in cat liver microsomes. MPA conjugation variation between cat liver microsomes was 3-fold for total conjugation and for phenol glucosidation, 6-fold for phenol glucuronidation, and 11-fold for acyl glucuronidation. Our results indicate that total MPA conjugation is quantitatively similar between liver microsomes from cats, dogs, and humans despite large differences in the conjugation pathways that are utilized by these species.
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影响因子：
1
作者：
Kyles, AE;Gregory, CR;Craigmill, AL
通讯作者：
Craigmill, AL
影响因子：
5.8
作者：
Bock, Karl Walter
通讯作者：
Bock, Karl Walter
DOI：
10.1016/j.cvsm.2013.05.002
发表时间：
2013-09-01
影响因子：
1.9
作者：
Court, Michael H.
通讯作者：
Court, Michael H.
影响因子：
1.6
作者：
Wang, A.;Smith, J. R.;Creevy, K. E.
通讯作者：
Creevy, K. E.
影响因子：
2.1
作者：
CARROCIAMPI, G;JURIMA, M;KALOW, W
通讯作者：
KALOW, W