ArticlePharmaceutical research2020
Drug Elimination Alteration in Acute Lymphoblastic Leukemia Mediated by Renal Transporters and Glomerular Filtration.
Article in Pharmaceutical research, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
3 citing papers in PubMed, 7 citations in OpenAlex.
- Population Pharmacokinetic Study of Cefathiamidine in Infants With Augmented Renal Clearance.Frontiers in pharmacology · 2021Article
- Downregulation of Renal MRPs Transporters in Acute Lymphoblastic Leukemia Mediated by the IL-6/STAT3/PXR Signaling Pathway.Journal of inflammation research · 2021Article
- Drug Transporters in the Kidney: Perspectives on Species Differences, Disease Status, and Molecular Docking.Frontiers in pharmacology · 2021Review
Corrections and comments
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Authors and funding
13 authors at 3 institutions in 1 country.
Funding
Abstract
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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