Drug Metabolism and Disposition
Papers 8973
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#1Jiayi Yin (ZJU: Zhejiang University)H-Index: 5
#2Fengcheng Li (ZJU: Zhejiang University)H-Index: 7
Last. Su Zeng (ZJU: Zhejiang University)H-Index: 35
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With the rapid progress in pharmaceutical experiments and clinical investigations, extensive knowledge of drug transporters (DTs) has accumulated, which is valuable data for the understanding of drug metabolism and disposition. However, such data is largely dispersed in the literature, which hampers its utility and significantly limits its possibility for comprehensive analysis. A variety of databases have, therefore, been constructed to provide DT-related data, and they were reviewed in this st...
#1Olena Anoshchenko (UW: University of Washington)H-Index: 2
#2Flavia Storelli (UW: University of Washington)H-Index: 4
Last. Jashvant D. Unadkat (UW: University of Washington)H-Index: 70
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Many women take drugs during their pregnancy to treat a variety of clinical conditions. To optimize drug efficacy and reduce fetal toxicity, it is important to determine or predict fetal drug exposure throughout pregnancy. Previously, we developed and verified a maternal-fetal physiologically based pharmacokinetic (m-f PBPK) model to predict fetal Kp,uu (unbound fetal plasma AUC/unbound maternal plasma AUC) of drugs that passively cross the placenta. Here, we used in vitro transport studies in T...
#1Rina Agustina (Kanazawa University)
#2Yusuke Masuo (Kanazawa University)H-Index: 12
Last. Yukio Kato (Kanazawa University)H-Index: 57
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Potential inhibition of the breast cancer resistance protein (BCRP), a drug efflux transporter, is a key issue during drug development, and the use of its physiological substrates as biomarkers can be advantageous to assess inhibition. In this study, we aimed to identify BCRP substrates by an untargeted metabolomic approach. Mice were orally administered lapatinib to inhibit BCRP in vivo, and plasma samples were assessed by liquid chromatography/time-of-flight/mass spectrometry (LC/TOF/MS), with...
#1Sara Shum (UW: University of Washington)H-Index: 6
#2Danny D. Shen (UW: University of Washington)H-Index: 51
Last. Nina Isoherranen (UW: University of Washington)H-Index: 44
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Fentanyl is an opioid analgesic used to treat obstetrical pain in parturient women through epidural or intravenous route, and unfortunately can also be abused by pregnant women. Fentanyl is known to cross the placental barrier, but how the route of administration and time after dosing affects maternal-fetal disposition kinetics at different stages of pregnancy is not well characterized. To address this knowledge gap, we developed a maternal-fetal physiologically based pharmacokinetic (mf-PBPK) m...
#1Sheri Smith (MSD: Merck & Co.)H-Index: 10
#2Michael Lyman (MSD: Merck & Co.)H-Index: 1
Last. Karsten Menzel (MSD: Merck & Co.)H-Index: 13
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Recognizing the challenges of determining the relative contribution of different drug metabolizing enzymes to the metabolism of slowly metabolized compounds, a cytochrome P450 reaction phenotyping (CRP) method, using co-cultured human hepatocytes (HEPATOPAC®), has been established. In this study, the emphasis on the relative contribution of different cytochrome P450 (CYP) isoforms was assessed by persistently inhibiting CYP isoforms over 7 days with human HEPATOPAC®. CYP isoform selective inhibi...
#1Koichi OmuraH-Index: 4
#2Keisuke MotokiH-Index: 2
Last. Takashi IwanagaH-Index: 14
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Dotinurad, a novel selective urate reabsorption inhibitor, is used to treat hyperuricemia. In humans, orally administered dotinurad is excreted mainly as glucuronide and sulfate conjugates in urine. To identify the isoforms of UDP-glucuronosyltransferase (UGT) and sulfotransferase (SULT) involved in dotinurad glucuronidation and sulfation, microsome and cytosol fractions of liver, intestine, kidney, and lung tissues (cytosol only) were analyzed along with recombinant human UGT and SULT isoforms....
#1Zivile Useckaite (Flinders University)
#2A. David Rodrigues (Pfizer)H-Index: 30
Last. Andrew Rowland (Flinders University)H-Index: 24
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Extracellular vesicles (EVs) are small, non-replicating, lipid encapsulated particles that contain a myriad of protein and nucleic acid cargo derived from their tissue of origin. The potential role of EV derived biomarkers to the study of drug metabolism and disposition (DMD) has gained attention in recent years. The key trait that makes EVs an attractive biomarker source is their capacity to provide comparable insights to solid organ biopsy through an appreciably less invasive collection proced...
#1Kazuaki Taguchi (Keio: Keio University)H-Index: 20
#2Yukitaka Hayashi (Keio: Keio University)H-Index: 1
Last. Akinobu Hamada (National Cancer Research Institute)H-Index: 3
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The clinically approved dose of nivolumab is 240 mg Q2W. However, previous studies have shown that baseline nivolumab clearance (CL) is associated with treatment outcomes in patients with solid cancers, thus motivating researchers to identify prognostic factors and indices influencing nivolumab CL. This study used chronic kidney disease model rats to investigate whether chronic renal impairment affected nivolumab CL and explored the surrogate markers associated with nivolumab CL. We observed tha...
#1Yifan Bao (UConn: University of Connecticut)H-Index: 4
#2Mi Phan (UConn: University of Connecticut)
Last. Xiao-bo Zhong (UConn: University of Connecticut)H-Index: 31
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Acetaminophen (APAP)-induced liver injury (AILI) is the leading cause of acute liver failure in the United States, but its impact on metabolism, therapeutic efficacy, and adverse drug reactions (ADRs) of co- and/or subsequent administered drugs are not fully investigated. The current work explored this field with a focus on the AILI-mediated alterations of cytochrome P450 (CYP)-mediated drug metabolism. Various levels of liver injury were induced in mice by treatment with APAP at 0, 200, 400, an...
#1Jessica L Beers (UNC: University of North Carolina at Chapel Hill)
#2Dong Fu (UNC: University of North Carolina at Chapel Hill)H-Index: 15
Last. Klarissa D. Jackson (UNC: University of North Carolina at Chapel Hill)H-Index: 3
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Cannabidiol (CBD) is a naturally occurring, non-psycho-toxic phytocannabinoid that has gained increasing attention as a popular consumer product and for its use in FDA-approved Epidiolex® (CBD oral solution) for the treatment of Lennox-Gastaut syndrome and Dravet syndrome. CBD was previously reported to be metabolized primarily by cytochrome P450 (CYP) 2C19 and CYP3A4, with minor contributions from UDP-glucuronosyltransferases. 7-Hydroxy-CBD (7-OH-CBD) is the primary active metabolite with equip...
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