Drug Elimination Alteration in Acute Lymphoblastic Leukemia Mediated by Renal Transporters and Glomerular Filtration
Drug Elimination Alteration in Acute Lymphoblastic Leukemia Mediated by Renal Transporters and Glomerular Filtration
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肾转运蛋白和肾小球滤过介导的急性淋巴细胞白血病的药物消除改变
DOI：
10.1007/s11095-020-02896-8
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发表时间：
2020-08
期刊：
影响因子：
--
通讯作者：
Wei Zhao
中科院分区：
文献类型：
--
作者：
Yue Zhou;Bin Du;Min Kan;Shang Chen;Bo-Hao Tang;Ai-Qing Nie;Pan-Pan Ye;Hai-Yan Shi;Guo-Xiang Hao;Xiu-Li Guo;Qiu-Ju Han;Yi Zheng;Wei Zhao
目的急性淋巴细胞白血病（ALL）的药物消除改变已被广泛报道。考虑到转运蛋白和肾小球滤过的影响，在不同程度上，药物处置，和可能的副作用，我们评估了ALL对主要的肾脏转运蛋白和肾小球滤过介导的药代动力学变化的影响，以及肾脏药物transporters.MethodsALL异种移植模型的建立和静脉注射肾转运蛋白和肾小球滤过底物分别在NOD/SCID小鼠。采用高效液相色谱-串联质谱法测定单次给药后底物的血浆浓度结果随着ALL的发展，MDR 1、OAT 3和OCT 2蛋白表达分别增加2.62倍、1.70倍和1.45倍，而MRP 2和MRP 4在ALL患者肾脏中的表达较对照组分别降低30.98%和45.28%。MDR 1介导的地高辛、OAT 3介导的呋塞米和OCT 2介导的二甲双胍的清除率分别增加了3.04倍、1.47倍和1.26倍。然而，MRP介导的甲氨蝶呤的清除率降低了39.5%。这些结果与mRNA表达一致。清除万古霉素和丁胺卡那霉素，肾小球滤过率的标志物，有2.14和1.64倍增加ALL小鼠，分别为conclusionsThe特定的肾脏转运蛋白和肾小球滤过在肾脏的改变提供了一个合理的解释为ALL的药代动力学变化。
PurposeDrug elimination alteration has been well reported in acute lymphoblastic leukemia (ALL). Considering that transporters and glomerular filtration influence, to different extents, the drug disposition, and possible side effects, we evaluated the effects of ALL on major renal transporters and glomerular filtration mediated pharmacokinetic changes, as well as expression of renal drug transporters.MethodsALL xenograft models were established and intravenously injected with substrates of renal transporters and glomerular filtration separately in NOD/SCID mice. The plasma concentrations of substrates, after single doses, were determined using high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS).ResultsWith the development of ALL, protein expression of MDR1, OAT3 and OCT2 were increased by 2.62-fold, 1.70-fold, and 1.45-fold, respectively, whereas expression of MRP2 and MRP4 were significantly decreased by 30.98% and 45.28% in the kidney of ALL groups compared with control groups. Clearance of MDR1-mediated digoxin, OAT3-mediated furosemide, and OCT2-mediated metformin increased by 3.04-fold, 1.47-fold, and 1.26-fold, respectively. However, clearance of MRPs-mediated methotrexate was reduced by 39.5%. These results are consistent with mRNA expression. Clearance of vancomycin and amikacin, as markers of glomerular filtration rate, had a 2.14 and 1.64-fold increase in ALL mice, respectively.ConclusionsThe specific alteration of renal transporters and glomerular filtration in kidneys provide a rational explanation for changes in pharmacokinetics for ALL.
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DOI：
10.1016/j.jchromb.2010.08.037
发表时间：
2010-10-15
影响因子：
3
作者：
Cheng, Chang;Liu, Shaorong;Hansel, Steven
通讯作者：
Hansel, Steven
影响因子：
7.8
作者：
El-Sheikh, Azza A. K.;Greupink, Rick;Russel, Frans G. M.
通讯作者：
Russel, Frans G. M.
影响因子：
1.8
作者：
Dijkstra, Jacob A.;Sturkenboom, Marieke G. G.;Alffenaar, Jan-Willem C.
通讯作者：
Alffenaar, Jan-Willem C.
DOI：
10.1002/jcph.736
发表时间：
2016-07
期刊：
The Journal of Clinical Pharmacology
影响因子：
--
作者：
J. Momper;S. Tsunoda;Joseph D. Ma
通讯作者：
J. Momper;S. Tsunoda;Joseph D. Ma
影响因子：
6.1
作者：
Kunin, Margarita;Holtzman, Eli J.;Dinour, Dganit
通讯作者：
Dinour, Dganit