Pharmacokinetic changes of norfloxacin based on expression of MRP2 after acute exposure to high altitude at 4300 m

Luo, Bingfeng; Wang, Rong; Li, Wenbin; Yang, Tao; Wang, Chang; Lu, Hui; Zhao, Andi; Zhang, Jilei; Zeng, Jia

doi:10.1016/j.biopha.2017.02.092

Cited by 14 publications

(3 citation statements)

References 48 publications

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“…Three major multidrug-resistant efflux transporters are abundantly expressed on THP-1 macrophages and mediate the transport of many quinolones [56][57][58]. For example, upregulation of MRP2 expression levels caused pharmacokinetic changes in the quinolone antibiotic norfloxacin, including downregulation of accumulation speed and degree parameters (AUC, k, and C max ) [59]. Verapamil and cyclosporin A mainly inhibit P-gp.…”

Section: Discussionmentioning

confidence: 99%

Ginsenoside 20(S)-Rh2 promotes cellular pharmacokinetics and intracellular antibacterial activity of levofloxacin against Staphylococcus aureus through drug efflux inhibition and subcellular stabilization

et al. 2021

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Intracellular Staphylococcus aureus (S. aureus) often causes clinical failure and relapse after antibiotic treatment. We previously found that 20(S)-ginsenoside Rh2 [20(S)-Rh2] enhanced the therapeutic effect of quinolones in a mouse model of peritonitis, which we attributed to the increased concentrations of quinolones within bacteria. In this study, we investigated the enhancing effect of 20(S)-Rh2 on levofloxacin (LVF) from a perspective of intracellular bacteria. In S. aureus 25923-infected mice, coadministration of LVF (1.5 mg/kg, i.v.) and 20(S)-Rh2 (25, 50 mg/kg, i.g.) markedly increased the survival rate, and decreased intracellular bacteria counts accompanied by increased accumulation of LVF in peritoneal macrophages. In addition, 20(S)-Rh2 (1, 5, 10 μM) dose-dependently increased the uptake and accumulation of LVF in peritoneal macrophages from infected mice without drug treatment. In a model of S. aureus 25923-infected THP-1 macrophages, we showed that 20(S)-Rh2 (1, 5, 10 μM) dose-dependently enhanced the intracellular antibacterial activity of LVF. At the cellular level, 20(S)-Rh2 increased the intracellular accumulation of LVF by inhibiting P-gp and BCRP. PK-PD modeling revealed that 20(S)-Rh2 altered the properties of the cell but not LVF. At the subcellular level, 20(S)-Rh2 did not increase the distribution of LVF in lysosomes but exhibited a stronger sensitizing effect in acidic environments. Molecular dynamics (MD) simulations showed that 20(S)-Rh2 improved the stability of the DNA gyrase-LVF complex in lysosome-like acidic conditions. In conclusion, 20(S)-Rh2 promotes the cellular pharmacokinetics and intracellular antibacterial activities of LVF against S. aureus through efflux transporter inhibition and subcellular stabilization, which is beneficial for infection treatment.

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Section: Discussionmentioning

confidence: 99%

Ginsenoside 20(S)-Rh2 promotes cellular pharmacokinetics and intracellular antibacterial activity of levofloxacin against Staphylococcus aureus through drug efflux inhibition and subcellular stabilization

et al. 2021

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“…This disease could decrease the protein level of OAT1, which may lead to an increased t 1/2 for some drugs ( Wang et al, 2020a ). In the high-altitude condition, the efflux drug transporters of MDR1 and MRP2 were increased, and clinicians should take it into consideration when drug prescription ( Luo et al, 2017 ). It is noteworthy that different viral infections bring different changes of the renal transporter levels.…”

Section: Effect Of Diseases On Transporter Expression and Functionmentioning

confidence: 99%

Drug Transporters in the Kidney: Perspectives on Species Differences, Disease Status, and Molecular Docking

et al. 2021

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The kidneys are a pair of important organs that excretes endogenous waste and exogenous biological agents from the body. Numerous transporters are involved in the excretion process. The levels of these transporters could affect the pharmacokinetics of many drugs, such as organic anion drugs, organic cationic drugs, and peptide drugs. Eleven drug transporters in the kidney (OAT1, OAT3, OATP4C1, OCT2, MDR1, BCRP, MATE1, MATE2-K, OAT4, MRP2, and MRP4) have become necessary research items in the development of innovative drugs. However, the levels of these transporters vary between different species, sex-genders, ages, and disease statuses, which may lead to different pharmacokinetics of drugs. Here, we review the differences of the important transports in the mentioned conditions, in order to help clinicians to improve clinical prescriptions for patients. To predict drug-drug interactions (DDIs) caused by renal drug transporters, the molecular docking method is used for rapid screening of substrates or inhibitors of the drug transporters. Here, we review a large number of natural products that represent potential substrates and/or inhibitors of transporters by the molecular docking method.

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“…When the body is in a hypoxic state, the blood flow and plasma flow of the kidney will be considerably reduced, and the permeability of renal glomerular capillaries will be enhanced accordingly, resulting in the change in glomerular filtration rate. In addition, pathological changes also occur in renal tubules in various renal tissues, and the secretion, absorption, and excretion functions of renal tubule epithelial cells are considerably affected (12)(13)(14)(15). Hypoxia leads to abnormal secretion of various hormones, such as catecholamine and antidiuretic hormone, resulting in the release of renin, which in turn promotes the formation of angiotensin II.…”

Section: Introductionmentioning

confidence: 99%

Effect of high-altitude hypoxia environment on uric acid excretion, Desmin protein level in podocytes, and Na+-K+- ATPase activity

Wang

et al. 2022

Cell Mol Biol (Noisy-le-grand)

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Pharmacokinetic changes of norfloxacin based on expression of MRP2 after acute exposure to high altitude at 4300 m

Cited by 14 publications

References 48 publications

Ginsenoside 20(S)-Rh2 promotes cellular pharmacokinetics and intracellular antibacterial activity of levofloxacin against Staphylococcus aureus through drug efflux inhibition and subcellular stabilization

Ginsenoside 20(S)-Rh2 promotes cellular pharmacokinetics and intracellular antibacterial activity of levofloxacin against Staphylococcus aureus through drug efflux inhibition and subcellular stabilization

Drug Transporters in the Kidney: Perspectives on Species Differences, Disease Status, and Molecular Docking

Effect of high-altitude hypoxia environment on uric acid excretion, Desmin protein level in podocytes, and Na+-K+- ATPase activity

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