1/17/2013. Dose Response and Concentration Response Analysis of Drug Effects

Size: px
Start display at page:

Download "1/17/2013. Dose Response and Concentration Response Analysis of Drug Effects"

Transcription

1 Dose Response and Concentration Response Analysis of Drug Effects Juan J. L. Lertora. M.D., Ph.D. IH Clinical Center January 17, 213 1

2 DOSE-EFFECT RELATIOSHIP The intensity and duration of a drug s effect(s) are a function of the drug dose and drug concentration at the effect site 2

3 Monitoring Dose-Effect Level Molecular (e.g, enzyme inhibition) Cellular (in vitro tissue culture, blood cells) Tissue or organ (in vitro or in vivo) Organism Endpoint used to measure effect may be different at each level Overall effect = sum of multiple drug effects and physiological response to drug effects 3

4 Endpoints to Monitor Drug Effect Farnesyltransferase Inhibitors for Cancer LEVEL EDPOIT Molecular Farnesyltransferase inhibition Cellular Proliferation rate, apoptosis Tumor Response (change in tumor size) Organism Survival, quality of life 4

5 Dose-Effect Endpoints Graded Continuous scale ( dose effect) Measured in a single biologic unit Relates dose to intensity of effect Quantal All-or-none pharmacologic effect Population studies Relates dose to frequency of effect 5

6 Erythropoietin and Anemia 25 2 Peak Hematocrit Increment [%] Eschbach et al. EJM 316:73-8, Erythropoietin Dose [units/kg] 6

7 Drug-Receptor Interactions Drug Drug-Receptor Complex Ligand-binding domain Effector domain Receptor k 1 k 2 Effect Effect = Maximal effect [Drug] K D + [Drug] (K D = k 2 /k 1 ) 7

8 Drug-Receptor Interactions Receptor-Effector system (signal-transduction pathway) G-protein coupled receptors Receptor-enzymes Ion channels uclear receptors 8

9 Dose-Effect Relationship Effect = Maximal effect [Drug] K D + [Drug] Effect = Maximal effect [Drug] K D + [Drug] Effect = Maximal effect if [Drug] >> K D 9

10 Graded Dose-Effect Curve 1 Maximal effect 8 % of Maximal Effect EC 5 [Drug] 1

11 Log Dose-Effect Curve 1 8 % of Maximal Effect EC [Drug] 11

12 Lidocaine Graded Dose-Effect 1 2 Analog Pain Score Ferrante et al. Anesth Analg 82:91-7, Lidocaine Blood Level [µg/ml] 12

13 Theophylline Dose-Effect 1 8 Relaxation % Control 6 4 PDE Inhibition 2 Rabe et al. Eur Respir J 8:637-42, Theophylline [µm] 13

14 Theophylline Pharmacodynamics FEV 1 (% normal) E max = 63% EC 5 = 1 mg/l Mitenko & Ogilvie EJM 289:6-3, Theophylline [mg/l] 14

15 Decrease in FPG from Placebo [mg/dl] 1/17/213 Metformin Dose-Response Decrease in HbA 1c from Placebo [%] Garber et al. Am J Med 12:491-7, Dose [mg/d] 15

16 Dose-Effect Parameters POTECY: The sensitivity of an organ or tissue to the drug EFFICACY: The maximum effect 16

17 Comparing Dose-Effect Curves 1 8 Drug A Drug B % of Maximal Effect 6 4 Drug C 2 Maximal effect [Drug] Effect = K D + [Drug] [Drug] 17

18 Thiopurine Cytotoxicity 1% Thioguanine Cytotoxic Effect 8% 6% 4% H 2 S H Mercaptopurine S H 2% Adamson et al. Leukemia Res 18:85-1, 1994 % Thiopurine [M] 18

19 Thiopurine Metabolic Activation SH MP SH TG 6 6 H H 2 H PRPP PRPP SH SH SH SH HO H 2 H 2 PO 4 CH 2 O PO 4 CH 2 O PO 4 CH 2 O (PO 4 ) 3 CH 2 O HO OH TIMP HO OH TXMP HO OH TGMP HO R (d)tgtp 19

20 Oral Mercaptopurine 5 4 AUC = Dose F Clearance MP AUC [µm hr] Balis et al. Blood 92: , MP Dose (mg/m 2 ) 2

21 Receptor-Mediated Effects 1 Agonist 8 % Maximum Effect Partial agonist Antagonist [Drug] 21

22 Receptor-Mediated Effects Agonist Partial agonist Antagonist Inverse agonist Receptors can exist in at least two conformations: active and inactive. An inverse agonist drives the equilibrium toward the inactive conformation. 22

23 Drug Interactions 1 Agonist 8 Agonist + competitive antagonist % of Maximal Effect 6 4 Agonist + non-competitive antagonist [Drug] 23

24 Graded Dose-Effect Analysis Identify the therapeutic dose/concentration Define site of drug action (receptor) Classify effect produced by drug-receptor interaction (agonist, antagonist) Compare the relative potency and efficacy of drugs that produce the same effect Assess mechanism of drug interactions 24

25 Quantal Dose-Effect Distribution 5 ED 5 4 # of Subjects Threshold Dose 25

26 Cumulative Dose-Effect Curve 1 8 Cumulative % of Subjects Dose 26

27 Cumulative Dose-Effect Study Dose Level o. of Subjects o. Responding % Response

28 Therapeutic and Toxic Effects 1 8 Therapeutic Toxic % Responding ED 99 ED Dose TD 1 TD 5 Indices 28

29 Therapeutic Indices Therapeutic Ratio = TD 5 ED 5 = 2.5 Certain Safety Factor = TD 1 ED 99 = 1.3 Standard Safety Margin = TD 1 - ED 99 ED 99 X 1 = 31% 29

30 Percent of patients 1/17/213 Digoxin Therapeutic Index Ventricular slowing Vomiting Digoxin (single oral dose, µg/kg) 3

31 Doxorubicin Cardiotoxicity 1..8 Probability of CHF von Hoff et al. Ann Intern Med 91:71-7, Total Doxorubicin Dose [mg/m 2 ] 31

32 Lidocaine Quantal Dose-Effect 1 8 ED 9 = 49 mg % Achieving Complete Analgesia ED 5 = 4 mg Ferrante et al. Anesth Analg 82:91-7, Total Lidocaine Dose (mg) 32

33 Antihypertensive Dose-Effect Dose Range [mg] Drug Early Studies Present Dose Lowest Effective Dose [mg] Propranolol Atenolol Hydrochlorothiazide Captopril Methyldopa Johnston Pharmacol Ther 55:53-93,

34 Antihypertensive Drugs 1 8 Desirable Dose Range Dose Range most often used % with Maximal Effect Adverse Effects Log Dose 34

35 Relating Dose to Effect In Vivo Dose Effect site Concentration Effect Pharmacokinetics Age Absorption Distribution Elimination Drug interactions Pharmacodynamics Tissue/organ sensitivity (receptor status) 35

36 Effect Compartment (PK/PD Model) Peripheral dx p dt k 12 C V c k 21 X p k 21 k 12 dc dt k V c (k 1 k 12 ) C k 21 Xp V c k Central k 1e Effect dc e dt k 1e C V c V e k e C e E(t) E C H max e EC H H 5 C e k 1 k e 36

37 Concentration and Effect vs. Time 1 on-steady State 1 8 Central Compartment 8 Conc./ Amount 6 4 Peripheral Compartment Effect 6 4 Effect [% of E max ] 2 Effect Compartment Time 37

38 Pharmacodynamic Models Fixed effect model Linear model Log-linear model E max model Sigmoid E max model Effect = E + S [Drug] Effect = I + S Log([Drug]) E max [Drug] H Effect = H EC5 + [Drug] H 38

39 Sigmoid E max PD Model Effect (%) Effect (%) H = H = 2 8 H = H =.5 H = EC 5 2 EC [Drug]

40 Hysteresis and Proteresis Loops Intensity of Drug Effect Hysteresis Loop (Counterclockwise) Equilibration delay in plasma and effect site conc. Formation of active metabolite Receptor up-regulation Intensity of Drug Effect Tolerance Proteresis Loop (Clockwise) Receptor tachyphylaxis Plasma Drug Concentration 4

41 Role of Dose-Effect Studies Drug development Site of action Selection of dose and schedule Potency, efficacy and safety Drug interactions Patient management Therapeutic drug monitoring Risk-benefit (therapeutic indices) 41

DOSE-EFFECT RELATIONSHIP

DOSE-EFFECT RELATIONSHIP DOSE-EFFECT RELATIONSHIP A fundamental principle of pharmacology is that the intensity of effect produced by a drug is a function of the quantity of drug administered (or the concentration of the drug

More information

Principles of Pharmacokinetics and Pharmacodynamics

Principles of Pharmacokinetics and Pharmacodynamics Principles of Pharmacokinetics and Pharmacodynamics Kevin K. Caldwell, Ph.D. PHARMACOKINETICS The actions of the body on the drug VS PHARMACODYNAMICS The actions of the drug on the body Katzung, 8th ed.,

More information

Session 14 Pharmacodynamics

Session 14 Pharmacodynamics Session 14 Pharmacodynamics 1 Receptor theory Objectives Relation between Drug concentration and response Drug potency & efficacy Antagonists competitive and unsurmountable Partial and full agonists Spare

More information

Carl Rosow, M.D., Ph.D. 1 HST-151. Lecture 1 - Principles of Pharmacology: Introduction

Carl Rosow, M.D., Ph.D. 1 HST-151. Lecture 1 - Principles of Pharmacology: Introduction Harvard-MIT Division of Health Sciences and Technology HST.151: Principles of Pharmocology Instructor: Dr. Carl Rosow Carl Rosow, M.D., Ph.D. 1 HST-151 Lecture 1 - Principles of Pharmacology: Introduction

More information

Nursing 113. Pharmacology Principles

Nursing 113. Pharmacology Principles Nursing 113 Pharmacology Principles 1. The study of how drugs enter the body, reach the site of action, and are removed from the body is called a. pharmacotherapeutics b. pharmacology c. pharmacodynamics

More information

Plasma Drug Concentration Time Profile Plotting Data

Plasma Drug Concentration Time Profile Plotting Data UNIT 2 PHARMACOKINETICS-BASIC CONSIDERATIONS Plasma Drug Concentration Time Profile Plotting Data S. SANGEETHA., M.PHARM., (Ph.d) Department of Pharmaceutics SRM College of Pharmacy SRM University INTRODUCTION

More information

LGD 6972: Glucagon Receptor Antagonist

LGD 6972: Glucagon Receptor Antagonist LGD 6972: Glucagon Receptor Antagonist Highly Potent, Orally Bioavailable, Small Molecule Glucagon Receptor Antagonist for the Treatment of Type 2 Diabetes Overview Diabetes is one of the largest and fastest

More information

Pharmacotherapy in the Elderly. Judy MY Wong

Pharmacotherapy in the Elderly. Judy MY Wong Pharmacotherapy in the Elderly Judy MY Wong judywong@berkeley.edu Percentage of population with prescription and number of medication per individual increase with age Definitions Pharmacology: pharmakon

More information

Drug Metabolism and Pharmacokinetics in Drug Discovery: A Primer For Bioanalytical Chemists, Part II

Drug Metabolism and Pharmacokinetics in Drug Discovery: A Primer For Bioanalytical Chemists, Part II Drug Metabolism and Pharmacokinetics in Drug Discovery: A Primer For Bioanalytical Chemists, Part II Chandrani Gunaratna, Ph.D. Bioanalytical Systems, Inc. 2701 Kent Avenue West Lafayette, IN 47906-1382

More information

Pharmacology skills for drug discovery. Why is pharmacology important?

Pharmacology skills for drug discovery. Why is pharmacology important? skills for drug discovery Why is pharmacology important?, the science underlying the interaction between chemicals and living systems, emerged as a distinct discipline allied to medicine in the mid-19th

More information

Farmacologia degli inibitori TK e mtor

Farmacologia degli inibitori TK e mtor Farmacologia degli inibitori TK e mtor Romano Danesi Professore ordinario di Farmacologia UOC Farmacologia Universitaria Azienda Ospedaliero-Universitaria Pisana Dipartimento di Medicina Interna Università

More information

BIOAVAILABILITY AND BIOEQIVALENCE

BIOAVAILABILITY AND BIOEQIVALENCE UNIT 5 BIOAVAILABILITY AND BIOEQIVALENCE S. SANGEETHA., M.PHARM., (Ph.d) Department of Pharmaceutics SRM College of Pharmacy SRM University BIOAVAILABILITY INTRODUCTION The bioavailability or systemic

More information

COMMITTEE FOR MEDICINAL PRODUCTS FOR HUMAN USE (CHMP)

COMMITTEE FOR MEDICINAL PRODUCTS FOR HUMAN USE (CHMP) European Medicines Agency Evaluation of Medicines for Human Use London, 22 February 2006 EMEA/CHMP/BMWP/31329/2005 COMMITTEE FOR MEDICINAL PRODUCTS FOR HUMAN USE (CHMP) ANNEX TO GUIDELINE ON SIMILAR BIOLOGICAL

More information

What is Bioavailability and Bioequivalence?

What is Bioavailability and Bioequivalence? What is Bioavailability and Bioequivalence? All generic medicines in New Zealand are approved by Medsafe and have been shown to be bioequivalent to innovator medicines, according to internationally accepted

More information

José E. Cavazos, MD PhD San Antonio VA Epilepsy Center of Excellence (VISN 17) Audie L. Murphy VA Medical Center. (210)

José E. Cavazos, MD PhD San Antonio VA Epilepsy Center of Excellence (VISN 17) Audie L. Murphy VA Medical Center. (210) José E. Cavazos, MD PhD San Antonio VA Epilepsy Center of Excellence (VISN 17) Audie L. Murphy VA Medical Center (210) 617-5161 cavazosj@uthscsa.edu AEDs and Drug Interactions Objectives: Identify at least

More information

NCT Preliminary Report: Phase I Dose Escalating Study to Evaluate the Safety,

NCT Preliminary Report: Phase I Dose Escalating Study to Evaluate the Safety, NCT02020291 Preliminary Report: Phase I Dose Escalating Study to Evaluate the Safety, Tolerability, Pharmacokinetic and Pharmacodynamic Profiles of Foxy-5 in Patients with Metastatic Breast, Colon or Prostate

More information

GT-020 Phase 1 Clinical Trial: Results of Second Cohort

GT-020 Phase 1 Clinical Trial: Results of Second Cohort GT-020 Phase 1 Clinical Trial: Results of Second Cohort July 29, 2014 NASDAQ: GALT www.galectintherapeutics.com 2014 Galectin Therapeutics inc. Forward-Looking Statement This presentation contains, in

More information

Statistics and Pharmacokinetics in Clinical Pharmacology Studies

Statistics and Pharmacokinetics in Clinical Pharmacology Studies Paper ST03 Statistics and Pharmacokinetics in Clinical Pharmacology Studies ABSTRACT Amy Newlands, GlaxoSmithKline, Greenford UK The aim of this presentation is to show how we use statistics and pharmacokinetics

More information

IV solutions may be given either as a bolus dose or infused slowly through a vein into the plasma at a constant or zero-order rate.

IV solutions may be given either as a bolus dose or infused slowly through a vein into the plasma at a constant or zero-order rate. د.شيماء Biopharmaceutics INTRAVENOUS INFUSION: IV solutions may be given either as a bolus dose or infused slowly through a vein into the plasma at a constant or zero-order rate. The main advantage for

More information

PHAR 7633 Chapter 19 Multi-Compartment Pharmacokinetic Models

PHAR 7633 Chapter 19 Multi-Compartment Pharmacokinetic Models Student Objectives for this Chapter PHAR 7633 Chapter 19 Multi-Compartment Pharmacokinetic Models To draw the scheme and write the differential equations appropriate to a multi-compartment pharmacokinetic

More information

Pre-clinical DMPK and relevance to the clinic

Pre-clinical DMPK and relevance to the clinic Pre-clinical DMPK and relevance to the clinic Richard Weaver Ph.D Managing Director and Founder of XenoGesis limited BioCity Nottingham Pennyfoot Street Nottingham, UK NG1 1GF richard.weaver@xenogesis.com

More information

Clinical Trial Results Database Page 1

Clinical Trial Results Database Page 1 Clinical Trial Results Database Page Sponsor Novartis Generic Drug Name BGT6 Therapeutic Area of Trial Advanced solid malignancies Approved Indication Investigational Study Number CBGT6A0 Title A phase

More information

Absorption and Half-Life. Objectives. Absorption. Extent of Absorption. Rate of Absorption

Absorption and Half-Life. Objectives. Absorption. Extent of Absorption. Rate of Absorption Absorption and Half-Life Nick Holford Dept Pharmacology & Clinical Pharmacology University of Auckland, New Zealand Objectives Understand the physiological determinants of rate and extent of absorption

More information

New anticoagulants: Monitoring or not Monitoring? Not Monitoring

New anticoagulants: Monitoring or not Monitoring? Not Monitoring The 2 nd World Congress on CONTROVERSIES IN HEMATOLOGY (COHEM) Barcelona, Spain September 6 8, 2012 New anticoagulants: Monitoring or not Monitoring? Not Monitoring Anna Falanga, MD Immunohematology and

More information

Medication Removal by Apheresis. Yanyun Wu, M.D., Ph.D. Yale University School of Medicine

Medication Removal by Apheresis. Yanyun Wu, M.D., Ph.D. Yale University School of Medicine Medication Removal by Apheresis Yanyun Wu, M.D., Ph.D. Yale University School of Medicine 1 Objectives Review basic pharmacokinetics and its relevance in drug removal by therapeutic apheresis (TPE) Review

More information

Clinical Trial Design. Sponsored by Center for Cancer Research National Cancer Institute

Clinical Trial Design. Sponsored by Center for Cancer Research National Cancer Institute Clinical Trial Design Sponsored by Center for Cancer Research National Cancer Institute Overview Clinical research is research conducted on human beings (or on material of human origin such as tissues,

More information

Clinical trials preclinical requirements. Clinical trials - legislation

Clinical trials preclinical requirements. Clinical trials - legislation Clinical trials preclinical requirements Mikael Andersson, PhD Senior Expert Medical Products Agency, Sweden Tallinn 9/10 2009 Clinical trials - legislation Directive 2001/20/EC Clinical trial directive

More information

The Clinical Trials Process an educated patient s guide

The Clinical Trials Process an educated patient s guide The Clinical Trials Process an educated patient s guide Gwen L. Nichols, MD Site Head, Oncology Roche TCRC, Translational and Clinical Research Center New York DISCLAIMER I am an employee of Hoffmann-

More information

OI PARP ΑΝΑΣΤΟΛΕΙΣ ΣΤΟΝ ΚΑΡΚΙΝΟ ΤΟΥ ΜΑΣΤΟΥ ΝΙΚΟΛΑΙΔΗ ΑΔΑΜΑΝΤΙΑ ΠΑΘΟΛΟΓΟΣ-ΟΓΚΟΛΟΓΟΣ Β ΟΓΚΟΛΟΓΙΚΗ ΚΛΙΝΙΚΗ ΝΟΣ. ΜΗΤΕΡΑ

OI PARP ΑΝΑΣΤΟΛΕΙΣ ΣΤΟΝ ΚΑΡΚΙΝΟ ΤΟΥ ΜΑΣΤΟΥ ΝΙΚΟΛΑΙΔΗ ΑΔΑΜΑΝΤΙΑ ΠΑΘΟΛΟΓΟΣ-ΟΓΚΟΛΟΓΟΣ Β ΟΓΚΟΛΟΓΙΚΗ ΚΛΙΝΙΚΗ ΝΟΣ. ΜΗΤΕΡΑ OI PARP ΑΝΑΣΤΟΛΕΙΣ ΣΤΟΝ ΚΑΡΚΙΝΟ ΤΟΥ ΜΑΣΤΟΥ ΝΙΚΟΛΑΙΔΗ ΑΔΑΜΑΝΤΙΑ ΠΑΘΟΛΟΓΟΣ-ΟΓΚΟΛΟΓΟΣ Β ΟΓΚΟΛΟΓΙΚΗ ΚΛΙΝΙΚΗ ΝΟΣ. ΜΗΤΕΡΑ Study Overview Inhibition of poly(adenosine diphosphate [ADP]-ribose) polymerase

More information

嘉 義 長 庚 醫 院 藥 劑 科 Speaker : 翁 玟 雯

嘉 義 長 庚 醫 院 藥 劑 科 Speaker : 翁 玟 雯 The Clinical Efficacy and Safety of Sodium Glucose Cotransporter-2 (SGLT2) Inhibitors in Adults with Type 2 Diabetes Mellitus 嘉 義 長 庚 醫 院 藥 劑 科 Speaker : 翁 玟 雯 Diabetes Mellitus : A group of diseases characterized

More information

MATHEMATICAL MODELS OF TUMOR GROWTH INHIBITION IN XENOGRAFT MICE AFTER ADMINISTRATION OF ANTICANCER AGENTS GIVEN IN COMBINATION

MATHEMATICAL MODELS OF TUMOR GROWTH INHIBITION IN XENOGRAFT MICE AFTER ADMINISTRATION OF ANTICANCER AGENTS GIVEN IN COMBINATION MATHEMATICAL MODELS OF TUMOR GROWTH INHIBITION IN XENOGRAFT MICE AFTER ADMINISTRATION OF ANTICANCER AGENTS GIVEN IN COMBINATION Nadia Terranova UNIVERSITÀ DI PAVIA New model development: course of action

More information

WHO guideline for abbreviated licensing pathways for certain biological therapeutic products

WHO guideline for abbreviated licensing pathways for certain biological therapeutic products WHO guideline for abbreviated licensing pathways for certain biological therapeutic products - Clinical evaluation - Martina Weise, MD Federal Institute for Drugs and Medical Devices, Germany General considerations

More information

Guidance for Industry

Guidance for Industry Guidance for Industry Exposure-Response Relationships Study Design, Data Analysis, and Regulatory Applications U.S. Department of Health and Human Services Food and Drug Administration Center for Drug

More information

Mathematical Expressions of the Pharmacokinetic and Pharmacodynamic Models implemented in the PFIM software

Mathematical Expressions of the Pharmacokinetic and Pharmacodynamic Models implemented in the PFIM software Mathematical Expressions of the Pharmacokinetic and Pharmacodynamic Models implemented in the PFIM software Anne Dubois, Julie Bertrand and France Mentré UMR738, INSERM, University Paris Diderot Programmer:

More information

NONCLINICAL EVALUATION FOR ANTICANCER PHARMACEUTICALS

NONCLINICAL EVALUATION FOR ANTICANCER PHARMACEUTICALS INTERNATIONAL CONFERENCE ON HARMONISATION OF TECHNICAL REQUIREMENTS FOR REGISTRATION OF PHARMACEUTICALS FOR HUMAN USE ICH HARMONISED TRIPARTITE GUIDELINE NONCLINICAL EVALUATION FOR ANTICANCER PHARMACEUTICALS

More information

Efficacy. Table 1. Overall Objective Response. Day 1 Day 2 Day 3 Day 4...Days 5-28. (vincristine infusion) (doxorubicin infusion)

Efficacy. Table 1. Overall Objective Response. Day 1 Day 2 Day 3 Day 4...Days 5-28. (vincristine infusion) (doxorubicin infusion) COST EFFECTIVENESS OF VS IN NEWLY DIAGNOSED MULTIPLE MYELOMA Mohamad A. Hussein, MD, 1 Mark Wildgust, PhD, 2 John Fastenau, MPH, RPh, 3 Catherine Tak Piech, MBA, 3 and the C2000-003 Study Group 1 The Cleveland

More information

Application for a Marketing Authorisation: Requirements and Criteria for the Assessment of QT Prolonging Potential

Application for a Marketing Authorisation: Requirements and Criteria for the Assessment of QT Prolonging Potential Application for a Marketing Authorisation: Requirements and Criteria for the Assessment of QT Prolonging Potential Bundesinstitut für Arzneimittel Dr. med. Clemens Mittmann Bundesinstitut für Arzneimittel

More information

A Study To Evaluate PF With Chemotherapy In Patients With Acute Myeloid Leukemia or Myelodysplastic Syndrome

A Study To Evaluate PF With Chemotherapy In Patients With Acute Myeloid Leukemia or Myelodysplastic Syndrome A service of the U.S. National Institutes of Health Trial record 1 of 5 for: efficacy of PF-04449913 Previous Study Return to List Next Study A Study To Evaluate PF-04449913 With Chemotherapy In Patients

More information

Clinical Study Synopsis for Public Disclosure

Clinical Study Synopsis for Public Disclosure abcd Clinical Study for Public Disclosure This clinical study synopsis is provided in line with s Policy on Transparency and Publication of Clinical Study Data. The synopsis - which is part of the clinical

More information

1: CLINICAL PHARMACOKINETICS

1: CLINICAL PHARMACOKINETICS : CLINICAL PHARMACOKINETICS General overview: clinical pharmacokinetics, 2 Pharmacokinetics, 4 Drug clearance (CL), 6 Volume of distribution (Vd), 8 The half-life (t½), 0 Oral availability (F), 2 Protein

More information

The CRM for ordinal and multivariate outcomes. Elizabeth Garrett-Mayer, PhD Emily Van Meter

The CRM for ordinal and multivariate outcomes. Elizabeth Garrett-Mayer, PhD Emily Van Meter The CRM for ordinal and multivariate outcomes Elizabeth Garrett-Mayer, PhD Emily Van Meter Hollings Cancer Center Medical University of South Carolina Outline Part 1: Ordinal toxicity model Part 2: Efficacy

More information

Medications for Alcohol and Opioid Use Disorders

Medications for Alcohol and Opioid Use Disorders Medications for Alcohol and Opioid Use Disorders Andrew J. Saxon, M.D. Center of Excellence in Substance Abuse Treatment and Education (CESATE) VA Puget Sound Health Care System Alcohol Pharmacotherapy

More information

Guidance for Industry

Guidance for Industry Guidance for Industry S9 Nonclinical Evaluation for Anticancer Pharmaceuticals U.S. Department of Health and Human Services Food and Drug Administration Center for Drug Evaluation and Research (CDER) Center

More information

Pharmacokinetics in Toxicology Research

Pharmacokinetics in Toxicology Research Pharmacokinetics in Toxicology Research Center for Human Health Assessment A Course on Physiologically Based Pharmacokinetic (PBPK) Modeling and Risk Assessment February 11 February 15, 2008 Copyright

More information

Volume of Distribution

Volume of Distribution 1 Volume of Distribution Nick Holford Dept Pharmacology & Clinical Pharmacology University of Auckland, New Zealand 2 Objectives Learn the definition of volume of distribution Understand the physiological

More information

1. Introduction 1.1. Scope of the Document 1.2. Relationships with Other Guidelines 2. Analytical Methods 3. Investigational Drug/Product 4. Complianc

1. Introduction 1.1. Scope of the Document 1.2. Relationships with Other Guidelines 2. Analytical Methods 3. Investigational Drug/Product 4. Complianc Clinical Pharmacokinetic Studies of Pharmaceuticals This document is an informal translation of the official text that was promulgated in Japanese on 1 June 2001 by Ministry of Health, Labour, and Welfare

More information

TGN 1412 Welche Änderungen haben sich für die Erstanwendung am Menschen aus Sicht des BfArM ergeben?

TGN 1412 Welche Änderungen haben sich für die Erstanwendung am Menschen aus Sicht des BfArM ergeben? TGN 1412 Welche Änderungen haben sich für die Erstanwendung am Menschen aus Sicht des BfArM ergeben? PD Dr. med. Thomas Sudhop Bundesinstitut für Arzneimittel, Bonn Bundesinstitut für Arzneimittel IMP

More information

ICH guideline S9 on nonclinical evaluation for anticancer pharmaceuticals

ICH guideline S9 on nonclinical evaluation for anticancer pharmaceuticals May 2010 EMA/CHMP/ICH/646107/2008 ICH guideline S9 on nonclinical evaluation for anticancer pharmaceuticals Step 5 Transmission to CHMP December 2008 Adoption by CHMP for release for consultation December

More information

Clinical Implementation of. Pharmacist-Managed Service. Kristine R. Crews, Pharm.D., BCPS St. Jude Children s Research Hospital

Clinical Implementation of. Pharmacist-Managed Service. Kristine R. Crews, Pharm.D., BCPS St. Jude Children s Research Hospital Clinical Implementation of Pharmacogenomics Through a Pharmacist-Managed Service Kristine R. Crews, Pharm.D., BCPS St. Jude Children s Research Hospital Objectives 1. Describe steps for incorporating pharmacogenomic

More information

SAFETY PHARMACOLOGY STUDIES FOR HUMAN PHARMACEUTICALS S7A

SAFETY PHARMACOLOGY STUDIES FOR HUMAN PHARMACEUTICALS S7A INTERNATIONAL CONFERENCE ON HARMONISATION OF TECHNICAL REQUIREMENTS FOR REGISTRATION OF PHARMACEUTICALS FOR HUMAN USE ICH HARMONISED TRIPARTITE GUIDELINE SAFETY PHARMACOLOGY STUDIES FOR HUMAN PHARMACEUTICALS

More information

GENERAL CONSIDERATIONS FOR CLINICAL TRIALS E8

GENERAL CONSIDERATIONS FOR CLINICAL TRIALS E8 INTERNATIONAL CONFERENCE ON HARMONISATION OF TECHNICAL REQUIREMENTS FOR REGISTRATION OF PHARMACEUTICALS FOR HUMAN USE ICH HARMONISED TRIPARTITE GUIDELINE GENERAL CONSIDERATIONS FOR CLINICAL TRIALS E8 Current

More information

Contact: Rebecca Wong (415) Questions and Answers Regarding Vidaza (azacitidine for injectable suspension) and Demethylating Agents

Contact: Rebecca Wong (415) Questions and Answers Regarding Vidaza (azacitidine for injectable suspension) and Demethylating Agents Contact: Rebecca Wong (415) 278-3319 Questions and Answers Regarding Vidaza (azacitidine for injectable suspension) and Demethylating Agents The recent approval of a third drug for the treatment of MDS

More information

Drug Prescribing in Kidney Disease: Initiative for Improved Dosing

Drug Prescribing in Kidney Disease: Initiative for Improved Dosing Drug Prescribing in Kidney Disease: Initiative for Improved Dosing Effects of impaired kidney function on drug pharmacokinetics and pharmacodynamics Section Leaders: William Bennett and Domenic Sica Passage

More information

Biological importance of metabolites. Safety and efficacy aspects

Biological importance of metabolites. Safety and efficacy aspects Biological importance of metabolites Safety and efficacy aspects Bernard Walther Technologie Servier Biological importance of metabolites Safety testing of drug metabolites Bioanalytical strategy Structural

More information

PKPD modelling of the relationship between testosterone and PSA in patients with prostate cancer during treatment with leuprorelin

PKPD modelling of the relationship between testosterone and PSA in patients with prostate cancer during treatment with leuprorelin PAGE 2015, Crete PKPD modelling of the relationship between testosterone and PSA in patients with prostate cancer during treatment with leuprorelin What is the optimal testosterone level? Nelleke Snelder,

More information

Advances In Chemotherapy For Hormone Refractory Prostate Cancer. TAX 327 study results & SWOG 99-16 study results presented at ASCO 2004

Advances In Chemotherapy For Hormone Refractory Prostate Cancer. TAX 327 study results & SWOG 99-16 study results presented at ASCO 2004 Ronald de Wit Rotterdam Cancer Institute The Netherlands Advances In Chemotherapy For Hormone Refractory Prostate Cancer TAX 327 study results & SWOG 99-16 study results presented at Slide 1 Prostate Cancer

More information

Discovery safety assessment of drug projects can be considered in two broad areas: target-related safety and chemical related safety.

Discovery safety assessment of drug projects can be considered in two broad areas: target-related safety and chemical related safety. Toxicology Skills for Drug Discovery Why is Toxicology in Drug Discovery important? The development of novel pharmaceuticals requires non-clinical safety studies to be performed on candidate drugs. Such

More information

Overview of Phase 1 Oncology Trials of Biologic Therapeutics

Overview of Phase 1 Oncology Trials of Biologic Therapeutics Overview of Phase 1 Oncology Trials of Biologic Therapeutics Susan Jerian, MD ONCORD, Inc. February 28, 2008 February 28, 2008 Phase 1 1 Assumptions and Ground Rules The goal is regulatory approval of

More information

COMMITTEE FOR PROPRIETARY MEDICINAL PRODUCTS (CPMP) NOTE FOR GUIDANCE ON THE PRE-CLINICAL EVALUATION OF ANTICANCER MEDICINAL PRODUCTS

COMMITTEE FOR PROPRIETARY MEDICINAL PRODUCTS (CPMP) NOTE FOR GUIDANCE ON THE PRE-CLINICAL EVALUATION OF ANTICANCER MEDICINAL PRODUCTS The European Agency for the Evaluation of Medicinal Products Human Medicines Evaluation Unit London, 23 July 1998 COMMITTEE FOR PROPRIETARY MEDICINAL PRODUCTS (CPMP) NOTE FOR GUIDANCE ON THE PRE-CLINICAL

More information

ICH Topic E 8 General Considerations for Clinical Trials. Step 5 NOTE FOR GUIDANCE ON GENERAL CONSIDERATIONS FOR CLINICAL TRIALS (CPMP/ICH/291/95)

ICH Topic E 8 General Considerations for Clinical Trials. Step 5 NOTE FOR GUIDANCE ON GENERAL CONSIDERATIONS FOR CLINICAL TRIALS (CPMP/ICH/291/95) European Medicines Agency March 1998 CPMP/ICH/291/95 ICH Topic E 8 General Considerations for Clinical Trials Step 5 NOTE FOR GUIDANCE ON GENERAL CONSIDERATIONS FOR CLINICAL TRIALS (CPMP/ICH/291/95) TRANSMISSION

More information

Alterações empresariais sustentadas pelo conceito de engenharia do Produto Patrício Soares da Silva, MD, PhD

Alterações empresariais sustentadas pelo conceito de engenharia do Produto Patrício Soares da Silva, MD, PhD Alterações empresariais sustentadas pelo conceito de engenharia do Produto Patrício Soares da Silva, MD, PhD 1 Summary Hypothesis Generation Candidate Development Commercialization Target Identification

More information

Proof-of-Concept Studies and the End of Phase IIa Meeting with the FDA

Proof-of-Concept Studies and the End of Phase IIa Meeting with the FDA Medpace Discovery Series presents Proof-of-Concept Studies and the End of Phase IIa Meeting with the FDA DR. JIM WEI: Today my topic is going to be Proof-of-Concept Studies and FDA End of Phase 2a Meetings

More information

IV Oxycodone: An alternative to IV Morphine for post-operative PCA use?

IV Oxycodone: An alternative to IV Morphine for post-operative PCA use? IV Oxycodone: An alternative to IV Morphine for post-operative PCA use? Damien Polioudakis Anaesthetic Registrar 25-09-2008 Acknowledgements Spiro Raftopoulos Hospital Specialist Representative - VIC What

More information

BRIVARACETAM. Paediatric Development in Partial Onset Seizures. 17 May 2016 HQ/0516/BRV/00022

BRIVARACETAM. Paediatric Development in Partial Onset Seizures. 17 May 2016 HQ/0516/BRV/00022 BRIVARACETAM Paediatric Development in Partial Onset Seizures 17 May 2016 HQ/0516/BRV/00022 Brivaracetam is indicated as adjunctive therapy in the treatment of partial onset seizures with or without secondary

More information

Aeterna Zentaris. 11 th Annual Needham Healthcare Conference April 3, 2012. Committed to cure

Aeterna Zentaris. 11 th Annual Needham Healthcare Conference April 3, 2012. Committed to cure 11 th Annual Needham Healthcare Conference April 3, 2012 Forward-Looking Statements This presentation contains forward-looking statements made pursuant to the safe harbor provisions of the U.S. Securities

More information

Treatment of Metastatic Breast Cancer: Endocrine Therapies. Robert W. Carlson, M.D. Professor of Medicine Stanford University

Treatment of Metastatic Breast Cancer: Endocrine Therapies. Robert W. Carlson, M.D. Professor of Medicine Stanford University Treatment of Metastatic Breast Cancer: Endocrine Therapies Robert W. Carlson, M.D. Professor of Medicine Stanford University MDACC Experience with FAC in Chemotherapy-Naive MBC Greenberg et al, J Clin

More information

Lead optimization services

Lead optimization services Lead optimization services The WIL Research Company (WRC) has extensive experience in fast track tailor-made screening strategies to help you with the challenging task of selecting your best candidate

More information

BSc in Medical Sciences with PHARMACOLOGY

BSc in Medical Sciences with PHARMACOLOGY BSc in Medical Sciences with PHARMACOLOGY Course Director Dr Christopher John Module Leaders Dr Robert Dickinson (Module 1) Dr Anabel Varela Carver (Module 2) Dr Sohag Saleh (Module 3) Course Administrator

More information

MOLECULAR PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS

MOLECULAR PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS MOLECULAR PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS R. M. Weinshilboum, M.D., Program Director L. Wang, M.D., Ph.D., Program Co-Director D. C. Mays, Ph.D., Associate Program Director Ph.D. Degree Course

More information

Correlation of Drug Levels and Outcomes in Phase III New Oral Anticoagulant (NOAC) Trials

Correlation of Drug Levels and Outcomes in Phase III New Oral Anticoagulant (NOAC) Trials Correlation of Drug Levels and Outcomes in Phase III New Oral Anticoagulant (NOAC) Trials October 26, 2015 CDER/OTS/OCP/DPM Jeffry Florian, Ph.D. CDER/OND/ODE1/DCRP Martin Rose, M.D. 1 Outline Overview

More information

Absorption of Drugs. Transport of a drug from the GI tract

Absorption of Drugs. Transport of a drug from the GI tract Absorption of Drugs Absorption is the transfer of a drug from its site of administration to the bloodstream. The rate and efficiency of absorption depend on the route of administration. For IV delivery,

More information

Guidance for Industry

Guidance for Industry Guidance for Industry Codevelopment of Two or More New Investigational Drugs for Use in Combination U.S. Department of Health and Human Services Food and Drug Administration Center for Drug Evaluation

More information

International Journal of Pharma and Bio Sciences LINAGLIPTIN- A NOVEL DPP-IV INHIBITOR

International Journal of Pharma and Bio Sciences LINAGLIPTIN- A NOVEL DPP-IV INHIBITOR International Journal of Pharma and Bio Sciences REVIEW ARTICLE PHARMACOLOGY LINAGLIPTIN- A NOVEL DPP-IV INHIBITOR Corresponding Author N.PRABAVATHY Department of Pharmacology, Mother Theresa Post Graduate

More information

Teriflunomide is the active metabolite of Leflunomide, a drug employed since 1994 for the treatment of rheumatoid arthritis (Baselt, 2011).

Teriflunomide is the active metabolite of Leflunomide, a drug employed since 1994 for the treatment of rheumatoid arthritis (Baselt, 2011). Page 1 of 10 ANALYTE NAME AND STRUCTURE TERIFLUNOMIDE Teriflunomide TRADE NAME Aubagio CATEGORY Antimetabolite TEST CODE PURPOSE Therapeutic Drug Monitoring GENERAL RELEVANCY BACKGROUND sclerosis. The

More information

Population Pharmacokinetics and Pharmacodynamics of Cisplatinum During Intraperitoneal Chemohyperthermia Using a Closed Abdominal Procedure

Population Pharmacokinetics and Pharmacodynamics of Cisplatinum During Intraperitoneal Chemohyperthermia Using a Closed Abdominal Procedure Population Pharmacokinetics and Pharmacodynamics of Cisplatinum During Intraperitoneal Chemohyperthermia Using a Closed Abdominal Procedure Eddy Cotte, Brigitte Tranchand, Annie-Claude Beaujard, François-Noël

More information

Factors Effecting Bioavailability Studies

Factors Effecting Bioavailability Studies Online Available at www.thepharmajournal.com THE PHARMA INNOVATION Factors Effecting Bioavailability Studies Bodavula Samba Siva Rao* Department of Pharmacy, Khammam college of pharmacy, Khammam, Andhra

More information

Longitudinal Modeling of Lung Function in Respiratory Drug Development

Longitudinal Modeling of Lung Function in Respiratory Drug Development Longitudinal Modeling of Lung Function in Respiratory Drug Development Fredrik Öhrn, PhD Senior Clinical Pharmacometrician Quantitative Clinical Pharmacology AstraZeneca R&D Mölndal, Sweden Outline A brief

More information

Combined Therapy with Insulin Plus Oral Agents. Is there Any Advantage?

Combined Therapy with Insulin Plus Oral Agents. Is there Any Advantage? Combined Therapy with Insulin Plus Oral Agents Is there Any Advantage? Matthew C. Riddle, M.D. Professor of Medicine Oregon Health & Science University Portland, Oregon Is there Any Advantage in Combined

More information

Comparison/Control Groups. Mary Foulkes, PhD Johns Hopkins University

Comparison/Control Groups. Mary Foulkes, PhD Johns Hopkins University This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike License. Your use of this material constitutes acceptance of that license and the conditions of use of materials on this

More information

Pharmacy Management Drug Policy

Pharmacy Management Drug Policy PAGE: Page 1 of 5 DESCRIPTION: Asthma is a heterogeneous syndrome that might be better described as a constellation of phenotypes, each with distinct cellular and molecular mechanisms, rather than as a

More information

Pharmacokinetics & Pharmacodynamics of Controlled Release Systems

Pharmacokinetics & Pharmacodynamics of Controlled Release Systems Pharmacokinetics & Pharmacodynamics of Controlled Release Systems Presented By: Govardhan.P Dept. of pharmaceutics, University College of Pharmaceutical Sciences, Kakatiya University, Warangal-506009.

More information

Accurately Measuring (And Reporting) Cardiotoxicity: Pitfalls & Proposed Solutions

Accurately Measuring (And Reporting) Cardiotoxicity: Pitfalls & Proposed Solutions Accurately Measuring (And Reporting) Cardiotoxicity: Pitfalls & Proposed Solutions Ronald Witteles, MD October 6, 2011 Stanford University School of Medicine Four Hypotheses Hypothesis 1: Product labeling

More information

Product Candidate: Eniluracil (EU)

Product Candidate: Eniluracil (EU) Eniluracil Summary Product Candidate: Eniluracil (EU) Oral Chemotherapy for Solid Tumors Irreversible inhibitor of DPD, the enzyme responsible for the rapid breakdown of 5-FU Developed as a potentiator

More information

Session 6 Clinical Trial Assessment Phase I Clinical Trial

Session 6 Clinical Trial Assessment Phase I Clinical Trial L1 Session 6 Clinical Trial Assessment Phase I Clinical Trial Presentation to APEC Preliminary Workshop on Review of Drug Development in Clinical Trials Celia Lourenco, PhD, Manager, Clinical Group I Office

More information

Bioequivalence Clinical Endpoint Studies

Bioequivalence Clinical Endpoint Studies Bioequivalence Clinical Endpoint Studies GPhA/FDA Fall Technical Conference Bethesda, MD, USA Oct. 29 2013 Murray P. Ducharme, PharmD, FCCP, FCP President and CEO, Learn and Confirm Inc. And, Professeur

More information

AKB-6548 clinical development overview early clinical studies (CI-0001 to CI-

AKB-6548 clinical development overview early clinical studies (CI-0001 to CI- AKB-6548 clinical development overview early clinical studies (CI-0001 to CI- 0004, and CI-0006) To date, AKB-6548 has been studied in 8 clinical trials across 4 separate patient populations: healthy volunteers

More information

PHARM 726. FUNDAMENTAL PHARMACOLOGY

PHARM 726. FUNDAMENTAL PHARMACOLOGY PHARM 726. FUNDAMENTAL PHARMACOLOGY Course Description: A basic pharmacology course in which principles underlying the actions of drugs are presented, including pharmacokinetics, drug-receptor interactions,

More information

Efficacy and Safety of Sublingual Sufentanil for the Management of Acute Pain Following Bunionectomy

Efficacy and Safety of Sublingual Sufentanil for the Management of Acute Pain Following Bunionectomy Efficacy and Safety of Sublingual Sufentanil for the Management of Acute Pain Following Bunionectomy Neil Singla, MD 1, Derek Muse, MD 2, Karen DiDonato, MSN, RN 3 and Pamela Palmer, MD, PhD 3 1 Lotus

More information

BL-8040: BEST-IN-CLASS CXCR4 ANTAGONIST FOR TREATMENT OF ONCOLOGICAL MALIGNANCIES

BL-8040: BEST-IN-CLASS CXCR4 ANTAGONIST FOR TREATMENT OF ONCOLOGICAL MALIGNANCIES BL-8040: BEST-IN-CLASS CXCR4 ANTAGONIST FOR TREATMENT OF ONCOLOGICAL MALIGNANCIES Clinical Development Program Prof. Moshe Phillip, MD VP Clinical & Medical Affairs 1 Rationale for BL-8040 Development

More information

Benefits in oncology. Mechanism of action

Benefits in oncology. Mechanism of action Mechanism of action The word cancer refers to a number of different diseases that share a common trait: the rapid, unrestrained growth and spread of cells that can invade and destroy surrounding tissues,

More information

CLINICAL TRIALS SHOULD YOU PARTICIPATE? by Gwen L. Nichols, MD

CLINICAL TRIALS SHOULD YOU PARTICIPATE? by Gwen L. Nichols, MD CLINICAL TRIALS SHOULD YOU PARTICIPATE? by Gwen L. Nichols, MD Gwen L. Nichols, M.D., is currently the Oncology Site Head of the Roche Translational Clinical Research Center at Hoffman- LaRoche. In this

More information

Day 3 Exercise 2 Parameter Optimization and Sensitivity Analysis: An Example Using a PBPK Model for Warfarin. April 19-23, 2010.

Day 3 Exercise 2 Parameter Optimization and Sensitivity Analysis: An Example Using a PBPK Model for Warfarin. April 19-23, 2010. Day 3 Exercise 2 Parameter Optimization and Sensitivity Analysis: An Example Using a PBPK Model for Warfarin A Course on Physiologically Based Pharmacokinetic (PBPK) Modeling and In Vitro to In Vivo Extrapolation

More information

What to do in case of hemorragia. L Camoin Jau Service d Hématologie APHM Marseille

What to do in case of hemorragia. L Camoin Jau Service d Hématologie APHM Marseille What to do in case of hemorragia with NOAC? L Camoin Jau Service d Hématologie APHM Marseille Disclosure Boehringer Bayer Daishi Sanofi BMS Pharmacodynamic and kinetic properties of new oral anticoagulants.

More information

Fexinidazole a new oral treatment for sleeping sickness update of development

Fexinidazole a new oral treatment for sleeping sickness update of development Fexinidazole a new oral treatment for sleeping sickness update of development SMe O 2 Me CH 2 O Antoine TARRAL Olaf Valverde Séverine Blesson Clélia Bardonneau Wilfried Mutumbo September 2011 Fexinidazole

More information

Scottish Medicines Consortium

Scottish Medicines Consortium Scottish Medicines Consortium pemetrexed 500mg infusion (Alimta ) No. (192/05) Eli Lilly 8 July 2005 The Scottish Medicines Consortium has completed its assessment of the above product and advises NHS

More information

Introduction to PK/PD modelling

Introduction to PK/PD modelling Introduction to PK/PD modelling with focus on PK and stochastic differential equations Stig Mortensen, Anna Helga Jónsdóttir, Søren Klim and Henrik Madsen November 19, 2008 DTU Informatics DTU Informatics

More information

Artemisinin in Cancer Treatment. Dr. Narendra P. Singh Department of Bioengineering University of Washington Seattle

Artemisinin in Cancer Treatment. Dr. Narendra P. Singh Department of Bioengineering University of Washington Seattle Artemisinin in Cancer Treatment Dr. Narendra P. Singh Department of Bioengineering University of Washington Seattle What is Artemisinin? Artemisinin is a sesquiterpene lactone isolated from the plant Artemesia

More information

Holy Family Hospital Dr Sarah Daniels April 2009

Holy Family Hospital Dr Sarah Daniels April 2009 Holy Family Hospital Dr Sarah Daniels April 2009 1 Topics to be covered Pharmacokinetics Pharmacodynamics Drug use in special groups Infants Children Elderly Pregnancy Polypharmacy 2 Pharmacokinetics Pharmacokinetics:

More information

DARATUMUMAB, A CD38 MONOCLONAL ANTIBODY IN PATIENTS WITH MULTIPLE MYELOMA - DATA FROM A DOSE- ESCALATION PHASE I/II STUDY

DARATUMUMAB, A CD38 MONOCLONAL ANTIBODY IN PATIENTS WITH MULTIPLE MYELOMA - DATA FROM A DOSE- ESCALATION PHASE I/II STUDY DARATUMUMAB, A CD38 MONOCLONAL ANTIBODY IN PATIENTS WITH MULTIPLE MYELOMA - DATA FROM A DOSE- ESCALATION PHASE I/II STUDY Torben Plesner, Henk Lokhorst, Peter Gimsing, Hareth Nahi, Steen Lisby, Paul Richardson

More information

Analytical Specifications RIVAROXABAN

Analytical Specifications RIVAROXABAN Page 1 of 9 ANALYTE NAME AND STRUCTURE - RIVAROXABAN SYNONYMS Xarelto CATEGORY Anticoagulant TEST CODE PURPOSE Therapeutic Drug Monitoring GENERAL RELEVANCY BACKGROUND Xarelto (rivaroxaban) is an orally

More information