Stable transfected HEK293-OATP cells for transporter analysis A model system for the assay of drug uptake.
|
|
|
- Frank Burns
- 6 years ago
- Views:
Transcription
1 Stable transfected HEK293-OATP cells for transporter analysis A model system for the assay of drug uptake. PRIMACYT Cell Culture Technology GmbH, Hagenower Str. 73, D Schwerin, Germany info@primacyt.com, Phone.: +49 (0) , Fax: +49 (0) PRIMACYT is a registered trade mark of PRIMACYT Cell Cure Technology GmbH - Copyright by PRIMACYT 1
2 The knowledge of drug affinity and drug-drug interaction (DDI) and the role of organic anion transporting polypeptides (OATPs) and other transporter proteins like P-glycoprotein (MDR1, P-gp, ABCB1) is a basic requirement in drug development and is also recommended by the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA). OATPs of the SLCO (former SLC21) superfamily are of fundamental importance in the transport of drugs across cell membranes, e.g. in intestine, liver, kidney, brain, skeleton muscle and placenta. Hepatic OATPs (OATP1B1, OATP1B3, OATP2B1) but also the sodium taurocholate cotransporting polypeptide (NTCP) are expressed at the sinusoidal membrane of human hepatocytes and transport several compounds into hepatocytes for biotransformation. In intestine, absorption of several compounds is mediated by e.g. OATP2B1 and the bile acid transporter ASBT (apical sodium-dependent bile salt transporter) which both are expressed at the brush border membrane. Primacyt utilizes well characterized stable transfected human embryonic kidney cells (HEK293) expressing different transporter proteins to study uptake of drugs and chemicals in vitro. 2
3 Characterization of the transfected transporter proteins using specific substrates and inhibitors HEK293 Substrates Inhibitors HEK293-OATP1A2 Taurocholic acid Fexofenadine Naringin HEK293-OATP1B1 Cremophor HEK293-OATP1B3 Estradiol 17ß-glucuronide Cremophor HEK293-OATP2B1 Atorvastatin Atorvastatin are trademarks of their respective owners. 3
4 Generation of stable transfected HEK293-OATP1A2 Coding sequence of SLCO1A2 was cloned into the retroviral expression vector pqcxin. HEK293 cells were infected according to the instructions of the manufacturer. HEK293 cells expressing recombinant OATP1A2 were selected by neomycin. Equivalent Procedures were used for OATP1B1, OATP1B3 and OATP2B1with corresponding SLCO genes. 4
5 Characterization of stable transfected HEK293-OATP1A2 Immunofluorescence and Western blot Immunofluorescence analysis of HEK293- OATP1A2 cells showed that OATP1A2 was localized in the plasma membrane. Western blot analysis of HEK293-OATP1A2 and HEK293-VC (vector control) cells showed a strong band at the molecular mass of approximately 70 kda in HEK293-OATP1A2 cells, which was not detectable in HEK293-VC cells. 5
6 Characterization of stable transfected HEK293-OATP1A2 Functionality test The uptake function of HEK293-OATP1A2 was characterized with Taurocholic acid and Estrone 3-sulfate as substrates. Fexofenadine and Naringin served as inhibitors of uptake. HEK293-OATP1A2 showed an uptake of Taurocholic acid with a Km of 80.5 µmol/l and Vmax of 20.5 pmol/mg min. HEK293-OATP1A2 showed an uptake of Estron 3-sulfate with a Km value of 23.1 µmol/l and a Vmax value of 87.8 pmol/ mg min. 6
7 Characterization of stable transfected HEK293-OATP1A2 Functionality test The uptake of by HEK293- OATP1A2 was efficiently inhibited by Fexofenadine with an IC50 of 77.9 µmol/l. The uptake of by HEK293- OATP1A2 was efficiently inhibited by Naringin with an IC50 of 21.3 µmol/l. 7
8 Characterization of the transfected transporter proteins using specific substrates and inhibitors HEK293 Substrates Inhibitors HEK293-OATP1A2 Taurocholic acid Fexofenadine Naringin HEK293-OATP1B1 Cremophor HEK293-OATP1B3 Estradiol 17ß-glucuronide Cremophor HEK293-OATP2B1 Atorvastatin Atorvastatin are trademarks of their respective owners. 8
9 Characterization of stable transfected HEK293-OATP1B1 Immunofluorescence and Western blot Immunofluorescence analysis of HEK293- OATP1B1 cells showed that OATP1B1 was localized in the plasma membrane. Western blot analysis of HEK293-OATP1B1 and HEK293-VC (vector control) cells showed a strong band at the molecular mass of approximately 84 kda in HEK293-OATP1B1 cells, which was not detectable in HEK293-VC cells. 9
10 Characterization of stable transfected HEK293-OATP1B1 Functionality test The uptake function of HEK293-OATP1B1 was characterized with and as substrates. and Cremophor served as inhibitors. HEK293-OATP1B1 showed an uptake of (BSP) with a Km value of 4.2 µmol/l and a Vmax value of 52.9 pmol/ mg min. The uptake of BSP was effectively inhibited by with an IC50 of 14.2 µmol/l. 10
11 Characterization of stable transfected HEK293-OATP1B1 Functionality test HEK293-OATP1B1 showed an uptake of Estrone 3-sulfate (E3S) with a Km value of 1.0 µmol/l and and a Vmax of 2.2 pmol/mg min). The uptake of E3S was effectively inhibited by Cremophor with IC50 of 0.2%. 11
12 Characterization of the transfected transporter proteins using specific substrates and inhibitors HEK293 Substrates Inhibitors HEK293-OATP1A2 Taurocholic acid Fexofenadine Naringin HEK293-OATP1B1 Cremophor HEK293-OATP1B3 Estradiol-17ß-glucuronide Cremophor HEK293-OATP2B1 Atorvastatin Atorvastatin are trademarks of their respective owners. 12
13 Characterization of stable transfected HEK293-OATP1B3 Immunofluorescence and Western blot Immunofluorescence analysis of HEK293- OATP1B3 cells showed that OATP1B3 was localized in the plasma membrane. Western blot analysis of HEK293-OATP1B3 and HEK293-VC (vector control) cells showed a strong band at the molecular mass of approximately 120 kda in HEK293-OATP1B3 cells, which was not detectable in HEK293-VC cells. 13
14 Characterization of stable transfected HEK293-OATP1B3 Functionality test The uptake function of HEK293-OATP1B3 was characterized with (BSP) as substrate. and Cremophor were used as inhibitors. HEK293-OATP1B3 showed an uptake of BSP with a Km value of 10.3 µmol/l and a Vmax value of 24.2 pmol/mg min. 14
15 Characterization of stable transfected HEK293-OATP1B3 Functionality test BSP uptake of HEK293-OATP1B3 cells could be efficiently inhibited by with an IC50 of 2.5 µmol/l. HEK293-OATP1B3 mediated BSP uptake could be efficiently inhibited by Cremophor with an IC50 of 0.005%. 15
16 Characterization of the transfected transporter proteins using specific substrates and inhibitors HEK293 Substrates Inhibitors HEK293-OATP1A2 Taurocholic acid Fexofenadine Naringin HEK293-OATP1B1 Cremophor HEK293-OATP1B3 Estradiol-17ß-glucuronide Cremophor HEK293 - OATP2B1 Atorvastatin Atorvastatin are trademarks of their respective owners. 16
17 Characterization of stable transfected HEK293-OATP2B1 Immunofluorescence and Western blot Immunofluorescence analysis of HEK293- OATP2B1 cells showed that OATP2B1 was localized in the plasma membrane. Western blot analysis of HEK293-OATP2B1 and HEK293-VC (vector control) cells showed a strong band at the molecular mass of approximately 85 kda in HEK293-OATP2B1 cells, which was not detectable in HEK293-VC cells. 17
18 Characterization of stable transfected HEK293-OATP2B1 Functionality test The uptake function of HEK293-OATP2B1 was characterized with and as substrates. Atorvastatin and served as inhibitors. HEK293-OATP2B1 showed an uptake of with a Km value of 11.1 µmol/l and a Vmax value of 22.4 pmol/ mg min. uptake by HEK293- OATP2B1 was efficiently inhibited by Atorvastatin with IC50 of 0.4 µmol/l. 18
19 Characterization of stable transfected HEK293-OATP2B1 Functionality test HEK293-OATP2B1 showed an uptake of with a Km of 21.9 µmol/l and a Vmax of 55.7 pmol/mg min. The uptake of could be efficiently inhibited by with an IC50 of 3.8 µmol/l. 19
20 Thank you See also our Blog on primacyt.com PRIMACYT Cell Culture Technology GmbH, Hagenower Str. 73, D Schwerin, Germany Phone.: +49 (0) , Fax: +49 (0) PRIMACYT is a registered trade mark of PRIMACYT Cell Culture Technology GmbH - Copyright by PRIMACYT 20
Use of in vitro cell assays and noninvasive imaging techniques to reduce animal experiments in drug development
Use of in vitro cell assays and noninvasive imaging techniques to reduce animal experiments in drug development J. Jia, M. Keiser, S. Oswald, W. Siegmund Department of Clinical Pharmacology, Ernst-Moritz-Arndt
Transporters DDI-2018
Transporters DDI-2018 Mark S. Warren, Ph.D. June 16, 2018 Senior Director of Assay Services DDI-2018: 21 st Conference on DDIs FDA guidance documents: A 21 year history 1997 2006 2012 2017 Each year, large
Strategy on Drug Transporter Investigation Why, How, Which & When. Jasminder Sahi
Strategy on Drug Transporter Investigation Why, How, Which & When Jasminder Sahi Intestine Drug Absorption PEPT1 OATPs MCTs AE2 Epithelial Cell MCTs MRP3 Liver Excretion via Liver Kidney MRPs OATPs N PT1
Welcome to the webinar... We will begin shortly
Welcome to the webinar... We will begin shortly Evaluation of Ketoconazole and Its Alternative Clinical CYP3A4/5 Inhibitors as Inhibitors of Drug Transporters: The In Vitro Effects of Ketoconazole, Ritonavir,
In vitro substrate-dependent inhibition of OATP1B1 and its impact on DDI prediction
SSX 3 rd Annual Conference (Oct 11, 2018) In vitro substrate-dependent inhibition of OATP1B1 and its impact on DDI prediction Yoshitane Nozaki, PhD DMPK Tsukuba Organic Anion Transporting Polypeptide (OATP)
Regulation of the cell surface expression and transport capacity of BSEP by small chemical molecules
Regulation of the cell surface expression and transport capacity of by small chemical molecules Hisamitsu Hayashi and Yuichi Sugiyama Dept. of Molecular Pharmacokinetics, Graduate School of Pharmaceutical
Complexities of Hepatic Drug Transport: How Do We Sort It All Out?
Complexities of Hepatic Drug Transport: How Do We Sort It All Out? Keith A. Hoffmaster Pfizer Research Technology Center Cambridge, MA NEDMDG 2005 Summer Symposium 06.08.2005 The Challenge Intestinal uptake
MODULE PHARMACOKINETICS WRITTEN SUMMARY
MODULE 2.6.4. PHARMACOKINETICS WRITTEN SUMMARY m2.6.4. Pharmacokinetics Written Summary 2013N179518_00 TABLE OF CONTENTS PAGE 1. BRIEF SUMMARY...4 2. METHODS OF ANALYSIS...5 3. ABSORPTION...6 4. DISTRIBUTION...7
Zurich Open Repository and Archive
University of Zurich Zurich Open Repository and Archive Winterthurerstr. 190 CH-8057 Zurich http://www.zora.uzh.ch Year: 2011 The Role of the Sodium-Taurocholate Cotransporting Polypeptide (NTCP) and of
Suitability of Digoxin as a P Glycoprotein Probe: Implications of Other Transporters on Sensitivity and Specificity
Review Suitability of Digoxin as a P Glycoprotein Probe: Implications of Other Transporters on Sensitivity and Specificity The Journal of Clinical Pharmacology XX(XX) 1 11 2013, The American College of
Interaction of baicalin with transporters
Interaction of baicalin with transporters PhD thesis Kalaposné Kovács Bernadett Semmelweis University Doctoral School of Pharmaceutical Sciences Supervisor: External Consultant: Official reviewers: Dr.
Determinants of Drug Disposition
Drug Transporters: In Vitro and Knockout Model Systems, Pharmacogenomics, and Clinical Relevance Richard B. Kim MD, FRCP(C) Professor & Chair, Division of Clinical Pharmacology Director, Centre for Clinical
Comparison Between the US FDA, Japan PMDA and EMA In Vitro DDI Guidance: Are we Close to Harmonization?
Comparison Between the US FDA, Japan PMDA and EMA In Vitro DDI Guidance: Are we Close to Harmonization? Brian Ogilvie, Ph.D. VP Scientific Consulting XenoTech, LLC bogilvie@xenotechllc.com 14 Jun, 2018
Thyroid Hormone Transport and Actions
Krassas GE, Rivkees SA, Kiess W (eds): Diseases of the Thyroid in Childhood and Adolescence. Pediatr Adolesc Med. Basel, Karger, 27, vol 11, pp 8 13 Thyroid Hormone Transport and Actions Ulla Feldt-Rasmussen,
SUPPLEMENTARY FIGURES
SUPPLEMENTARY FIGURES Supplementary Figure 1: immunoprecipitation with anti-casr antibody The Casr protein was expressed in transiently transfected HEK cells. Cell lysates from HEK cells were subjected
Evaluation of Proposed In Vivo Probe Substrates and Inhibitors for Phenotyping Transporter Activity in Humans
Supplement Article Evaluation of Proposed In Vivo Probe Substrates and Inhibitors for Phenotyping Transporter Activity in Humans The Journal of Clinical Pharmacology (2016), 56(S7) S82 S98 C 2016, The
In vitro and in silico Predictions of Hepatic Transporter-Mediated Drug Clearance and Drug-Drug Interactions in vivo
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Pharmacy 193 In vitro and in silico Predictions of Hepatic Transporter-Mediated Drug Clearance and Drug-Drug Interactions in
Classification of Inhibitors of Hepatic Organic Anion Transporting Polypeptides (OATPs): Influence of Protein Expression on Drug Drug Interactions
pubs.acs.org/jmc Classification of Inhibitors of Hepatic Organic Anion Transporting Polypeptides (OATPs): Influence of Protein Expression on Drug Drug Interactions Maria Karlgren,*,, Anna Vildhede, Ulf
Till David och Calle
Till David och Calle List of Papers This thesis is based on the following papers, which are referred to in the text by their Roman numerals assigned below. I II III Bergman, E., Forsell, P., Tevell, A.,
Drug Drug and Drug Transporter Interactions as Obstacles for Absorption
Drug Drug and Drug Transporter Interactions as Obstacles for Absorption Reza Fassihi Ph.D., AAPS Fellow Professor of Biopharmaceutics and Industrial Pharmacy Temple University, School of Pharmacy Presented
Current Approaches and Applications of Phenotyping Methods for Drug Metabolizing Enzymes and Transporters
Current Approaches and Applications of Phenotyping Methods for Drug Metabolizing Enzymes and Transporters Uwe Fuhr, University Hospital Cologne 1 Definition Phenotyping is quantifying the in vivo activity
Biochemical and Molecular Toxicology. The Role of Transporters (Phase III) in Xenobiotic Disposition
Biochemical and Molecular Toxicology ENVR 442/TOXC 442/BIOC 442 The Role of Transporters (Phase III) in Xenobiotic Disposition Kim L.R. Brouwer, PharmD, PhD William R. Kenan Distinguished Professor and
DRUG-DRUG INTERACTIONS OF GLECAPREVIR AND PIBRENTASVIR WITH PRAVASTATIN, ROSUVASTATIN, OR DABIGATRAN ETEXILATE
DRUG-DRUG INTERACTIONS OF GLECAPREVIR AND PIBRENTASVIR WITH PRAVASTATIN, ROSUVASTATIN, OR DABIGATRAN ETEXILATE Matthew P. Kosloski, Weihan Zhao, Hong Li, Stanley Subhead Wang, Calibri Joaquin 14pt, Valdes,
T Eley, Y-H Han, S-P Huang, B He, W Li, W Bedford, M Stonier, D Gardiner, K Sims, P Balimane, D Rodrigues, RJ Bertz
IN VIVO AND IN VITRO ASSESSMENT OF ASUNAPREVIR (ASV; BMS-650032) AS AN INHIBITOR AND SUBSTRATE OF ORGANIC ANION TRANSPORT POLYPEPTIDE (OATP) TRANSPORTERS IN HEALTHY VOLUNTEERS T Eley, Y-H Han, S-P Huang,
Department of Internal Medicine and the Department of Pathology. Wake Forest University
Bile Acid Transporters Paul A. Dawson, Tian Lan, Anuradha Rao Department of Internal Medicine and the Department of Pathology. Wake Forest University School of Medicine. Winston-Salem, NC 27157 Corresponding
Department of Internal Medicine and Department of Pathology, Wake Forest University School of Medicine, Winston-Salem, NC 27157
thematic review Thematic Review Series: Bile Acids Bile acid transporters Paul A. Dawson, 1 Tian Lan, and Anuradha Rao Department of Internal Medicine and Department of Pathology, Wake Forest University
Pharmacokinetic Determinants of Statin-Induced Myopathy
Pharmacokinetic Determinants of Statin-Induced Myopathy Rommel G. Tirona, B.Sc.Phm., Ph.D. Departments of Physiology & Pharmacology and Medicine The University of Western Ontario, London, Ontario, Canada
Role of metabolism in Drug-Induced Liver Injury (DILI) Drug Metab Rev. 2007;39(1):
Role of metabolism in Drug-Induced Liver Injury (DILI) Drug Metab Rev. 2007;39(1):159-234 Drug Metab Rev. 2007;39(1):159-234 Drug Metab Rev. 2007;39(1):159-234 A schematic representation of the most relevant
ROLE OF MEMBRANE TRANSPORTERS IN DRUG DELIVERY, DRUG DISPOSITION AND DRUG-DRUG INTERACTIONS. A DISSERTATION IN Pharmaceutical Sciences and Chemistry
ROLE OF MEMBRANE TRANSPORTERS IN DRUG DELIVERY, DRUG DISPOSITION AND DRUG-DRUG INTERACTIONS A DISSERTATION IN Pharmaceutical Sciences and Chemistry Presented to the Faculty of University of Missouri-Kansas
Building innovative drug discovery alliances. Hepatic uptake and drug disposition o in vitro and in silico approaches
Building innovative drug discovery alliances Hepatic uptake and drug disposition o in vitro and in silico approaches Dr Beth Williamson Evotec AG, 2017 Outline Importance of predicting clearance In vitro
Current and Emerging Transporter Regulatory Themes in Drug Development: Relevance to Understanding PK/PD, DDIs, and Toxicity
Current and Emerging Transporter Regulatory Themes in Drug Development: Relevance to Understanding PK/PD, DDIs, and Toxicity Maciej Zamek-Gliszczynski, Ph.D. 1940 s Probenecid & anion secretion 1950 s
Cryo Characterization Report (CCR)
Human Cryopreserved Hepatocytes Lot number: HUM4061B Date: October 19, 2014 Cryo Characterization Report (CCR) Lot Overview Qualification Catalog Number Quantity Cryopreserved human hepatocytes, Qualyst
Itraconazole and Clarithromycin as Ketoconazole Alternatives for Clinical CYP3A Inhibition Studies to Quantify Victim DDI Potential
Itraconazole and Clarithromycin as Ketoconazole Alternatives for Clinical CYP3A Inhibition Studies to Quantify Victim DDI Potential Alice Ban Ke, Ph.D. Consultant & Scientific Advisor Simcyp Limited Alice.Ke@certara.com
Hepatic uptake of the magnetic resonance imaging contrast agent Gd-EOB-DTPA, role of human organic anion transporters
DMD This Fast article Forward. has not been Published copyedited on and formatted. April 20, The 2010 final as version doi:10.1124/dmd.110.032862 may differ from this version. DMD # 32862 Hepatic uptake
Thematic Review Series: Intestinal Lipid Metabolism: New Developments and Current Insights. Intestinal transport and metabolism of bile acids
thematic review Thematic Review Series: Intestinal Lipid Metabolism: New Developments and Current Insights Intestinal transport and metabolism of bile acids Paul A. Dawson 1 and Saul J. Karpen Department
What Can Be Learned from Recent New Drug Applications? A Systematic Review of Drug
Title What Can Be Learned from Recent New Drug Applications? A Systematic Review of Drug Interaction Data for Drugs Approved by the U.S. FDA in 2015 Jingjing Yu, Zhu Zhou, Katie H. Owens, Tasha K. Ritchie,
Pathophysiology of Bile Secretion
Pathophysiology of Bile Secretion Martin C. Carey, D.Sc., M.D. Division of Gastroenterology, Brigham and Women s Hospital and Department of Medicine, Harvard Medical School Boston, MA, U.S.A. Functions
Exploiting BDDCS and the Role of Transporters
Exploiting BDDCS and the Role of Transporters (Therapeutic benefit of scientific knowledge of biological transporters, understanding the clinical relevant effects of active transport on oral drug absorption)
Quantitative Evaluation of the Effect of P-Glycoprotein on Oral Drug Absorption
Quantitative Evaluation of the Effect of P-Glycoprotein on Oral Drug Absorption -Assessment of Drug Permeability to Rat Small Intestine- College of Pharmacy, Setsunan University, Osaka, Japan Yoshiyuki
Prediction of in vivo hepatic clearance and DDI of OATP substrates: Comparison of different in vitro approaches. Yuichi Sugiyama
Prediction of in vivo hepatic clearance and DDI of OATP substrates: Comparison of different in vitro approaches. Yuichi Sugiyama Sugiyama Laboratory, RIKEN Innovation Center, RIKEN, Research Cluster for
ATP-Binding-Cassette Transporters in Biliary Efflux and Drug-Induced Liver Injury
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Pharmacy 172 ATP-Binding-Cassette Transporters in Biliary Efflux and Drug-Induced Liver Injury JENNY M. PEDERSEN ACTA UNIVERSITATIS
Publications directly related to the thesis
Publications directly related to the thesis Investigation of interactions between ABC transporters and their lipid environment - Effect of membrane cholesterol content on the function of human ABCG2 (BCRP/MXR)
Involvement of transporters in the hepatic uptake and biliary excretion of
DMD This Fast article Forward. has not been Published copyedited on and formatted. April 19, The 2006 final as version doi:10.1124/dmd.105.008938 may differ from this version. Involvement of transporters
The role of organic anion transporting polypeptides in drug absorption, distribution, excretion and drug-drug interactions
Expert Opinion on Drug Metabolism & Toxicology ISSN: 1742-5255 (Print) 1744-7607 (Online) Journal homepage: http://www.tandfonline.com/loi/iemt20 The role of organic anion transporting polypeptides in
The Role of Drug Transporters in Statin-Induced Myopathy
Western University Scholarship@Western Electronic Thesis and Dissertation Repository December 2012 The Role of Drug Transporters in Statin-Induced Myopathy Michael J. Knauer The University of Western Ontario
Fundamentals of Membrane Transporters and their Role in In Vivo PK/PD of Drugs
Fundamentals of Membrane Transporters and their Role in In Vivo PK/PD of Drugs Jash Unadkat, Ph.D. Department of Pharmaceutics University of Washington Seattle, WA 98195 http://depts.washington.edu/pceut/faculty_research/faculty_members/unadkat_jashvant.html
Influence of Non-Steroidal Anti-Inflammatory Drugs on Organic Anion Transporting Polypeptide (OATP) 1B1- and OATP1B3- Mediated Drug Transport
0090-9556/11/3906-1047 1053$25.00 DRUG METABOLISM AND DISPOSITION Vol. 39, No. 6 Copyright 2011 by The American Society for Pharmacology and Experimental Therapeutics 37622/3688980 DMD 39:1047 1053, 2011
Brian C. Ferslew. Chapel Hill Approved by: Dhiren Thakker. Mary F. Paine. A. Sidney Barritt. Kim L.R. Brouwer. Jo Ellen Rodgers.
IMPORTANCE OF HEPATIC TRANSPORTERS, INCLUDING BASOLATERAL EFFLUX PROTEINS, IN DRUG DISPOSITION: IMPACT OF PHOSPHOLIPIDOSIS AND NON-ALCOHOLIC STEATOHEPATITIS Brian C. Ferslew A dissertation submitted to
Symposium: Target or Avoid?
RSC Drug Transporters Symposium: Target or Avoid? Thursday 13 th November 2014 The exploitation ti and under-exploitation exploitation of transporters in drug discovery Steve Alexander, Pharmacology, School
DRUG METABOLISM AND PHARMACOKINETICS (DMPK) Lena Gustavsson, H. Lundbeck A/S, November 2015
DRUG METABOLISM AND PHARMACOKINETICS (DMPK), H. Lundbeck A/S, LEGU@lundbeck.com November 2015 DMPK in Drug Discovery and Development Agenda Introduction Optimizing pharmacokinetic properties Absorption
Investigation of Probe Substrates to Assess Hepatic Transport Function. Brandon Swift
Investigation of Probe Substrates to Assess Hepatic Transport Function by Brandon Swift A dissertation submitted to the faculty of the University of North Carolina at Chapel Hill in partial fulfillment
Supplementary Figure 1. AdipoR1 silencing and overexpression controls. (a) Representative blots (upper and lower panels) showing the AdipoR1 protein
Supplementary Figure 1. AdipoR1 silencing and overexpression controls. (a) Representative blots (upper and lower panels) showing the AdipoR1 protein content relative to GAPDH in two independent experiments.
IN VIVO AND IN VITRO METHODS TO DETERMINE BILIARY CLEARANCE OF DRUGS IN HUMANS. by Giulia Ghibellini
IN VIVO AND IN VITRO METHODS TO DETERMINE BILIARY CLEARANCE OF DRUGS IN HUMANS by Giulia Ghibellini A dissertation submitted to the faculty of the University of North Carolina at Chapel Hill in partial
PHARMACOKINETIC INTERACTIONS AND PHARMACOGENETICS OF ALISKIREN
Department of Clinical Pharmacology University of Helsinki Finland PHARMACOKINETIC INTERACTIONS AND PHARMACOGENETICS OF ALISKIREN Tuija Tapaninen ACADEMIC DISSERTATION To be presented, with permission
Supporting information
Supporting information Intracellular drug bioavailability: a new predictor of system dependent drug disposition Mateus, André 1* ; Treyer, Andrea 1* ; Wegler, Christine 1,2 ; Karlgren, Maria 1 ; Matsson,
INTERACTION OF BAICALIN WITH TRANSPORTERS. Bernadett Kalaposné Kovács
INTERACTION OF BAICALIN WITH TRANSPORTERS PhD thesis Bernadett Kalaposné Kovács Doctoral School of Pharmaceutical Sciences Semmelweis University Supervisor: Dr. Imre Klebovich, D.Sc Official reviewers:
Zurich Open Repository and Archive. Genetic determinants of drug-induced cholestasis and intrahepatic cholestasis of pregnancy
University of Zurich Zurich Open Repository and Archive Winterthurerstr. 190 CH-8057 Zurich http://www.zora.uzh.ch Year: 2010 Genetic determinants of drug-induced cholestasis and intrahepatic cholestasis
Strep-tag HRP Detection Kit (Horse Radish Peroxidase)
Strep-tag HRP Detection Kit (Horse Radish Peroxidase) General protocol for the detection of Strep-tag fusion proteins Last date of revision April 2013 Version PR16-0006 www.strep-tag.com For research use
TARGETING ORGANIC ANION TRANSPORTING POLYPEPTIDES IN CANCER TO IMPROVE DIAGNOSTICS AND THERAPY Amanda Lynne Hays
TARGETING ORGANIC ANION TRANSPORTING POLYPEPTIDES IN CANCER TO IMPROVE DIAGNOSTICS AND THERAPY By 2012 Amanda Lynne Hays Submitted to the graduate degree program in Pharmacology, Toxicology and Therapeutics
Effect of cyclosporine A and tacrolimus on OATP1B1 mediated transport of atorvastatin in an in vitro whole cell model
Effect of cyclosporine A and tacrolimus on OATP1B1 mediated transport of atorvastatin in an in vitro whole cell model Behnaz Zabihyan Department of Pharmacy, Faculty of Medicine University of Tromsø Department
Title. CitationCancer Letters, 260(1-2): Issue Date Doc URL. Type. File Information. fluorescent probes
Title Rapid screening of antineoplastic candidates for the fluorescent probes Yamaguchi, Hiroaki; Kobayashi, Minako; Okada, Masahi Author(s) Junichi; Hishinuma, Takanori; Mano, Nariyasu CitationCancer
Causes and Consequences of Variability in Drug Transporter Activity in Pediatric Drug Therapy
Supplement Article Causes and Consequences of Variability in Drug Transporter Activity in Pediatric Drug Therapy The Journal of Clinical Pharmacology (2016), 56(S7) S173 S192 C 2016, The American College
The importance of pharmacogenetics in the treatment of epilepsy
The importance of pharmacogenetics in the treatment of epilepsy Öner Süzer and Esat Eşkazan İstanbul University, Cerrahpaşa Faculty of Medicine, Department of Pharmacology and Clinical Pharmacology Introduction
NIH Public Access Author Manuscript Drug Metab Dispos. Author manuscript; available in PMC 2009 January 1.
NIH Public Access Author Manuscript Published in final edited form as: Drug Metab Dispos. 2008 January ; 36(1): 61 64. doi:10.1124/dmd.107.017319. Multidrug Resistance-Associated Protein 2 (Mrp2) is Primarily
Investigating Transporter-Mediated Drug-Drug Interactions Using a Physiologically Based Pharmacokinetic Model of Rosuvastatin
Citation: CPT Pharmacometrics Syst. Pharmacol. (2017) 6, 228 238; VC 2017 ASCPT All rights reserved doi:10.1002/psp4.12168 ORIGINAL ARTICLE Investigating Transporter-Mediated Drug-Drug Interactions Using
Digestive System. Part 3
Digestive System Part 3 Digestion Ingested materials must be broken down for absorption Majority of absorption in small intestine Water and alcohol in stomach mucosa Some salts and vitamins in large intestine
Mechanistic Modeling of Pitavastatin Disposition in Sandwich-Cultured Human Hepatocytes: A Proteomics-Informed Bottom-Up Approach s
Supplemental material to this article can be found at: http://dmd.aspetjournals.org/content/suppl/2016/02/03/dmd.115.066746.dc1 1521-009X/44/4/505 516$25.00 http://dx.doi.org/10.1124/dmd.115.066746 DRUG
Chunying Gao, Hongjian Zhang, Zitao Guo, Tiangeng You, Xiaoyan Chen, and Dafang Zhong
1521-009X/12/4010-2009 2020$25.00 DRUG METABOLISM AND DISPOSITION Vol. 40, No. 10 Copyright 2012 by The American Society for Pharmacology and Experimental Therapeutics 47183/3797028 DMD 40:2009 2020, 2012
Pharmacogenetics and Pharmacokinetics
Chapter 2 Pharmacogenetics and Pharmacokinetics Mauro Saivezzo/ShutterStock, Inc. L earning O bjectives Upon completion of this chapter, the student will be able to: 1. Recognize the influence of genetic
Effect of OATP-binding on the prediction of biliary excretion
Effect of OATP-binding on the prediction of biliary excretion Article (Accepted Version) Sharifi, Mohsen and Ghafourian, Taravat (2017) Effect of OATP-binding on the prediction of biliary excretion. Xenobiotica,
Digoxin is not a Substrate for Organic Anion Transporting Polypeptide Transporters
DMD Fast This article Forward. has not Published been copyedited on and August formatted. 17, The 2011 final version as doi:10.1124/dmd.111.040816 may differ from this version. Digoxin is not a Substrate
Anti-DC-SIGN/CD209 murine monoclonal antibodies
Anti-DC-SIGN/CD209 murine monoclonal antibodies DC-SIGN (DC Specific, ICAM-3 Grabbing, Nonintegrin) / CD209 and L-SIGN (liver/lymph node-specific ICAM-3-grabbing nonintegrin CD299/ DC-SIGNR (DC-SIGN-related
In Vitro and In Vivo Interaction Studies Between Lesinurad, a Selective Urate Reabsorption Inhibitor, and Major Liver or Kidney Transporters
Clin Drug Investig (2016) 36:443 452 DOI 10.1007/s40261-016-0386-y ORIGINAL RESEARCH ARTICLE In Vitro and In Vivo Interaction Studies Between Lesinurad, a Selective Urate Reabsorption Inhibitor, and Major
Review Article. Abstract
vv Chemistry Group Open Journal of Chemistry DOI http://dx.doi.org/10.17352/ojc.000006 CC By Srinivas Maddi 1 *, Thirumaleswara Goud 2 and Pratima Srivastava 1 1 GVK Biosciences PVT LTD, Nacharam, Hyderabad,
Zurich Open Repository and Archive
University of Zurich Zurich Open Repository and Archive Winterthurerstr. 190 CH-8057 Zurich http://www.zora.uzh.ch Year: 2008 Pharmacogenetics of OATP (SLC21/SLCO), OAT and OCT (SLC22) and PEPT (SLC15)
Department of Pediatrics. Division of Gastroenterology, Hepatology, and Nutrition. Emory
Intestinal Transport and Metabolism of Bile Acids Paul A. Dawson* and Saul J. Karpen Department of Pediatrics. Division of Gastroenterology, Hepatology, and Nutrition. Emory University. Atlanta, GA 30322.
Overview of Intestinal Drug Metabolism and Transport
Overview of Intestinal Drug Metabolism and Transport Kenneth E. Thummel, PhD, University of Washington, Seattle, WA DDI Conference June 20, 2016 Proximal Intestinal Microanatomy Key DMEs and Transporters
Influence of Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) on. OATP1B1- and OATP1B3-mediated Drug Transport
DMD Fast This article Forward. has not been Published copyedited on and March formatted. 9, The 2011 final version as doi:10.1124/dmd.110.037622 may differ from this version. DMD # 37622 Influence of Non-Steroidal
Biopharmaceutics Drug Disposition Classification System (BDDCS) --- Its Impact and Application
Biopharmaceutics Drug Disposition Classification System (BDDCS) --- Its Impact and Application Leslie Z. Benet, Ph.D. Professor of Bioengineering and Therapeutic Sciences Schools of Pharmacy and Medicine
Received December 2, 2005; accepted June 5, 2006
0090-9556/06/3409-1575 1581$20.00 DRUG METABOLISM AND DISPOSITION Vol. 34, No. 9 Copyright 2006 by The American Society for Pharmacology and Experimental Therapeutics 8748/3132909 DMD 34:1575 1581, 2006
Assessment of inhibitory effect of many therapeutically important drugs on bile acid transport by NTCP, BSEP and other transporters
ct 6, 26 Falk Symposium 155; XIX International Bile Acid Meeting Assessment of inhibitory effect of many therapeutically important drugs on bile acid transport by NTCP, BSEP and other transporters Kazuya
Multiple Transporters Affect the Disposition of Atorvastatin and Its Two Active Hydroxy Metabolites: Application of in Vitro and ex Situ Systems
0022-3565/06/3162-762 771$20.00 THE JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS Vol. 316, No. 2 Copyright 2006 by The American Society for Pharmacology and Experimental Therapeutics 93088/3076593
Critical review of the literature on drug interactions
Critical review of the 2015-2016 literature on drug interactions Katie Owens, BPharm PhD Research Scientist II Drug Interaction Database (DIDB) Program Dept. of Pharmaceutics University of Washington 19
Development of a Cell-Based High-Throughput Assay to Screen for Inhibitors of Organic Anion Transporting Polypeptides 1B1 and 1B3
Current Chemical Genomics, 2010, 4, 1-8 1 Open Access Development of a Cell-Based High-Throughput Assay to Screen for Inhibitors of Organic Anion Transporting Polypeptides 1B1 and 1B3 Chunshan Gui 1, Amanda
Hepatic Transporter Proteins involved in Bile Formation
Bile salt synthesis Hepatic Transporter Proteins involved in Bile Formation Basolateral membrane transporter proteins fx: NTCP uptake of bile salts OATP bulky organic anions Canalicular membrane transporter
INTERACTIONS OF ANTIRETROVIRAL PROTEASE INHIBITORS WITH HEPATIC TRANSPORT PROTEINS: MECHANISMS OF DRUG-INDUCED LIVER INJURY. LaToya M.
INTERACTIONS OF ANTIRETROVIRAL PROTEASE INHIBITORS WITH HEPATIC TRANSPORT PROTEINS: MECHANISMS OF DRUG-INDUCED LIVER INJURY LaToya M. Griffin A dissertation submitted to the faculty of the University of
DMD # Chunying Gao, Michael Z. Liao, Lyrialle W. Han, Kenneth E. Thummel, and Qingcheng. Mao*
Hepatic transport of 25-hydroxyvitamin D 3 conjugates: a mechanism of 25-hydroxyvitamin D 3 delivery to the intestinal tract Chunying Gao, Michael Z. Liao, Lyrialle W. Han, Kenneth E. Thummel, and Qingcheng
Wen Zhao,* Jeremiah D. Zitzow, David J. Ehresman, Shu-Ching Chang, John L. Butenhoff,,1 Jameson Forster, and Bruno Hagenbuch* ABSTRACT
TOXICOLOGICAL SCIENCES, 146(2), 2015, 363 373 doi: 10.1093/toxsci/kfv102 Advance Access Publication Date: May 21, 2015 Research Article Na 1 /Taurocholate Cotransporting Polypeptide and Apical Sodium-Dependent
Pharmacologic Considerations when using DAAs in Cirrhosis
Pharmacologic Considerations when using DAAs in Cirrhosis Jennifer J. Kiser, PharmD Assistant Professor University of Colorado Denver 1 st International Workshop on the Optimal Use of DAAs in Liver Transplant
CO-ADMINISTRATION WITH GRAZOPREVIR AND ELBASVIR HAS NO EFFECT ON PRAVASTATIN EXPOSURE BUT INCREASES ROSUVASTATIN EXPOSURE IN HEALTHY SUBJECTS
CO-ADMINISTRATION WITH GRAZOPREVIR AND ELBASVIR HAS NO EFFECT ON PRAVASTATIN EXPOSURE BUT INCREASES ROSUVASTATIN EXPOSURE IN HEALTHY SUBJECTS Luzelena Caro 1, William L. Marshall 1, Hwa-Ping Feng 1, Zifang
Transporters and Drug-Drug Interactions: Important Determinants of Drug Disposition and Effects s
Supplemental Material can be found at: /content/suppl/2013/05/23/65.3.944.dc1.html 1521-0081/65/3/944 966$25.00 http://dx.doi.org/10.1124/pr.113.007518 PHARMACOLOGICAL REVIEWS Pharmacol Rev 65:944 966,
REVIEW TRANSPORT OF BILE ACIDS IN HEPATIC AND NON-HEPATIC TISSUES
The Journal of Experimental Biology 204, 1673 1686 (2001) Printed in Great Britain The Company of Biologists Limited 2001 JEB3185 1673 REVIEW TRANSPORT OF BILE ACIDS IN EPATIC AND NON-EPATIC TISSUES MARIE
Enzyme- and Transporter-Mediated Beverage Drug Interactions: An Update on Fruit Juices and Green Tea
Review Enzyme- and Transporter-Mediated Beverage Drug Interactions: An Update on Fruit Juices and Green Tea The Journal of Clinical Pharmacology 2015, XX(XX) 1 19 2015, The American College of Clinical
Why do patients take herbs and nutritional supplements?
Why do patients take herbs and nutritional supplements? Dissatisfaction with conventional medicine > Relieve cancer-related symptoms > Treat adverse effects of anticancer drugs > Treat cancer > Promote
"The Transporter Company" VP, Global Operations & Services
SOLVO Biotechnology "The Transporter Company" Bill Johnson, Ph.D. VP, Global Operations & Services Presentation Topics SOLVO "The Transporter Company" Membrane Transporters, Barriers Regulatory Background
Application of LC-MS/MS Method for Evaluating Rosuvastatin Affinity with OATP1B1 and OATP2B1 in vitro
Asian Journal of Chemistry; Vol. 26, No. 2 (214), 335-341 http://dx.doi.org/1.14233/ajchem.214.15376 Application of LC-MS/MS Method for Evaluating Rosuvastatin Affinity with OATP1B1 and OATP2B1 in vitro
Citrus Juices Inhibit the Function of. Human Organic Anion Transporting Polypeptide OATP-B
DMD Fast This article Forward. has not Published been copyedited on and January formatted. The 7, 2005 final version as doi:10.1124/dmd.104.002337 may differ from this version. Citrus Juices Inhibit the
Biopharmaceutics Drug Disposition Classification System (BDDCS) and Its Application in Drug Discovery and Development
Biopharmaceutics Drug Disposition Classification System (BDDCS) and Its Application in Drug Discovery and Development Leslie Z. Benet, Ph.D. Professor of Bioengineering and Therapeutic Sciences University
University of Groningen. The enterohepatic circulation of bile salts in health and disease Hulzebos, Christian Victor
University of Groningen The enterohepatic circulation of bile salts in health and disease Hulzebos, Christian Victor IMPORTANT NOTE: You are advised to consult the publisher's version (publisher's PDF)
Hepatocyte polarity: constitutive and functional characteristics and pathological appearance in liver diseases
23 1 2011 1 Chinese Bulletin of Life Sciences Vol. 23, No. 1 Jan., 2011 ( 100730) Q813; R575.1 A Hepatocyte polarity: constitutive and functional characteristics and pathological appearance in liver diseases