scholarly journals Impact of renal impairment and human organic anion transporter inhibition on pharmacokinetics, safety and tolerability of relebactam combined with imipenem and cilastatin

2020 ◽  
Vol 86 (5) ◽  
pp. 944-957
Author(s):  
Pratik Bhagunde ◽  
Francheska Colon‐Gonzalez ◽  
Yang Liu ◽  
Jin Wu ◽  
Shiyao Sherrie Xu ◽  
...  
Keyword(s):  
Renal Impairment ◽  
Organic Anion ◽  
Organic Anion Transporter ◽  
Anion Transporter

scholarly journals Effects of Renal Impairment on the Pharmacokinetics of Morinidazole: Uptake Transporter-Mediated Renal Clearance of the Conjugated Metabolites

2014 ◽  
Vol 58 (7) ◽  
pp. 4153-4161 ◽  
Author(s):  
Kan Zhong ◽  
Xiuli Li ◽  
Cen Xie ◽  
Yifan Zhang ◽  
Dafang Zhong ◽  
...  
Keyword(s):  
Renal Impairment ◽  
Renal Clearance ◽  
Healthy Subjects ◽  
Severe Renal Impairment ◽  
Organic Anion ◽  
Organic Anion Transporter ◽  
Anion Transporter ◽  
Plasma And Urine Samples ◽  
Conjugated Metabolites

ABSTRACTMorinidazole is a novel 5-nitroimidazole antimicrobial drug that undergoes extensive metabolism in humans viaN+-glucuronidation (N+-glucuronide ofS-morinidazole [M8-1] andN+-glucuronide ofR-morinidazole [M8-2]) and sulfation (sulfate conjugate of morinidazole [M7]). Our objectives were to assess the effects of renal impairment on the pharmacokinetics (PK) of morinidazole and to elucidate the potential mechanisms. In this parallel-group study, healthy subjects and patients with severe renal impairment received an intravenous infusion of 500 mg of morinidazole. Plasma and urine samples were collected and analyzed. The areas under the plasma concentration-time curves (AUC) for M7, M8-1, and M8-2 were 15.1, 20.4, and 17.4 times higher, respectively, in patients with severe renal impairment than in healthy subjects, while the AUC for morinidazole was 1.5 times higher. The urinary recovery of the major metabolites was not significantly different between the two groups over 0 to 48 h, but the renal clearances of M7, M8-1, and M8-2 in patients were 85.3%, 92.5%, and 92.2% lower, respectively.In vitrotransporter studies revealed that M7 is a substrate for organic anion transporter 1 (OAT1) and OAT3 (Km= 28.6 and 54.0 μM, respectively). Only OAT3 transported M8-1 and M8-2. Morinidazole was not a substrate for the transporter-transfected cells examined. These results revealed that the function or activity of renal uptake transporters might be impaired in patients with severe renal impairment, which accounted for dramatically increased plasma exposure and reduced renal clearance of the conjugated metabolites of morinidazole, the substrates of renal transporters in patients. It will help clinicians to adjust the dose in patients with severe renal impairment and to predict possible transporter-based drug-drug interactions.

scholarly journals Chinese Herbal Formulas Si-Wu-Tang and Er-Miao-San Synergistically Ameliorated Hyperuricemia and Renal Impairment in Rats Induced by Adenine and Potassium Oxonate

2015 ◽  
Vol 37 (4) ◽  
pp. 1491-1502 ◽  
Author(s):  
Yongping Guo ◽  
Qian Jiang ◽  
Dingkun Gui ◽  
Niansong Wang
Keyword(s):  
Uric Acid ◽  
Renal Impairment ◽  
Serum Uric Acid ◽  
Organic Anion ◽  
Organic Anion Transporter ◽  
Protective Effects ◽  
Chinese Herbal ◽  
Renal Histopathology ◽  
Anion Transporter ◽  
Potassium Oxonate

Background/Aims: Hyperuricemia is an independent risk factor for chronic kidney disease and cardiovascular disease. Here, we examined the combined protective effects of Chinese herbal formula Si-Wu-Tang and Er-Miao-San on hyperuricemia and renal impairment in rats. Methods: Rats were randomly divided into normal rats, hyperuricemic rats, and hyperuricemic rats orally administrated with benzbromarone (4.5 mg·kg-1·d-1), Si-Wu-Tang (3.78 g·kg-1·d-1) and Si-Wu-Tang plus Er-Miao-San (6.48 g·kg-1·d-1) for 4 weeks. Hyperuricemic rats were orally gavaged with adenine (0.1 g·kg-1·d-1) and potassium oxonate (1.5 g·kg-1·d-1) daily for 4 weeks. Serum uric acid, creatinine, total cholesterol (TCH), triglyceride and blood urea nitrogen (BUN) concentrations, as well as urinary uric acid and microalbuminuria were measured weekly. Serum xanthine oxidase (XOD) activity and renal histopathology were also evaluated. The renal expression of organic anion transporter 1 (OAT1) and organic anion transporter 3 (OAT3) was detected by western blot. Results: Si-Wu-Tang plus Er-Miao-San lowered serum uric acid, creatinine, triglyceride and BUN levels to a greater degree than did Si-Wu-Tang alone. Si-Wu-Tang plus Er-Miao-San ameliorated microalbuminuria and renal histopathology, as well as decreased serum TCH concentration and XOD activity in hyperuricemic rats. Combination of Si-Wu-Tang and Er-Miao-San also led to a greater increase in OAT1 and OAT3 expression than did Siwutang alone. Conclusion: Si-Wu-Tang and Er-Miao-San synergistically ameliorated hyperuricemia and renal impairment in rats through upregulation of OAT1 and OAT3.

Characterization of hepatobiliary organic anion transporter regulation in the Zucker rat

2004 ◽  
Vol 42 (08) ◽  
Author(s):  
A Geier ◽  
CG Dietrich ◽  
C Gartung ◽  
F Lammert ◽  
HE Wasmuth ◽  
...  
Keyword(s):  
Organic Anion ◽  
Organic Anion Transporter ◽  
Zucker Rat ◽  
Anion Transporter

Human Renal Organic Anion Transporter 1-Dependent Uptake and Toxicity of Mercuric-Thiol Conjugates in Madin-Darby Canine Kidney Cells

2003 ◽  
Vol 63 (3) ◽  
pp. 590-596 ◽  
Author(s):  
Amy G. Aslamkhan ◽  
Yong-Hae Han ◽  
Xiao-Ping Yang ◽  
Rudolfs K. Zalups ◽  
John B. Pritchard
Keyword(s):  
Organic Anion ◽  
Organic Anion Transporter ◽  
Kidney Cells ◽  
Madin Darby Canine Kidney ◽  
Anion Transporter ◽  
Darby Canine Kidney ◽  
Canine Kidney
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