DOCSLIB.ORG

Clinical Pharmacology—The Quarterback of Drug

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Clinical Pharmacology—The Quarterback of Drug Clinical Pharmacology— The Quarterback of Drug Development PEER REVIEWED Ellen Leinfuss; Julie Bullock [DOI: 10.14524/CR-17-0016] A quarterback’s job is to direct the team toward the end zone Clinical pharmacology accounts for about 50% and score as many points as possible. Considered the leader of of a drug label. Its scope ranges from facilitating the team, the quarterback is often responsible for calling the play; the discovery of new target molecules to deter- mining the effects of drugs in different popula- however, the quarterback isn’t just responsible for knowing how to tions. From both industry-wide and regulatory do his job—he has to know the responsibilities of every player on perspectives, the levers of clinical pharmacology the field to win the game. can address the huge challenges of late-stage attrition and increase the efficiency of drug development in the quest to bring the “ball” into the end zone. June 2017 20 Clinical Researcher Clinical pharmacology accounts for about 50% of a drug label FIGURE 1: Role of Clinical Pharmacology in the Drug Label Warning Warnings Contraindications and precautions Special dosage instructions Special populations Adverse Drug reactions interactions Clinical Dosage and pharmacology administration PK: ADME WHAT IS CLINICAL PHARMACOLOGY? in drug development due to scientific challenges in predicting efficacy and safety or characterizing Clinical pharmacology is the science of the sources of drug response variability at early, less relationship between drugs and humans. It focuses expensive stages of discovery. on drug action, and incorporates pharmacolog- Clinical pharmacology can help stakeholders ical principles and techniques into the clinical to address these challenges and improve decision development cycle. It is increasingly leveraged making at critical drug development milestones, at all phases of development with an eye toward whether in early proof-of-concept phases (preclin- delivering the right drug to the right patient with the ical through IIa), or in the later stages where more right dose at the right time. robust risk and efficacy profiles are established Clinical pharmacology contributes to a range of (Phase IIb through III). clinical decisions, and features prominently in the Clinical pharmacology tools, methods, and drug label, as shown in Figure 1. frameworks (e.g., mechanistic or quantitative) span A recent paper1 by a group of scientists from distinct subspecialties, and can have a significant the U.S. Food and Drug Administration (FDA), impact at the interface of nonclinical and clinical academia, and industry clearly articulated how phases. They can greatly reduce uncertainty clinical pharmacology methods and a quanti- related to therapeutic targets, dosing, and patient tative framework can improve the efficiency of populations in which the novel compound may drug development and evaluation. That paper, have the most efficacy.1 “Improving the Tools of Clinical Pharmacology: Goals for 2017 and Beyond,” points to limitations Clinical Researcher 21 June 2017 FIGURE 2: Clinical Pharmacology Toolkit According to Kristofer Baumgartner, a strategic communications officer with FDA, MIDD already Population has resulted in shorter trials with fewer patients, PK fewer postmarketing studies, and tailored drug dosing. “The use of modeling and simulation has the potential to make the interpretation of Clinical Trial Exposure- data more efficient, improve the prediction of Simulation Response drug safety and efficacy, and explain variable patient responses,” Baumgartner told BioCentury in September 2016. “MIDD approaches, such as ClinPharm physiologically based pharmacokinetic (PBPK), Quantitative dose- and exposure-response, and disease-drug- Toolkit trial modeling and simulation approaches have been used to inform a variety of drug development and public health decisions, such as drug dosing QSP PBPK and use in certain subpopulations.”2 Key items in the clinical pharmacology toolkit include: • Pharmacometrics Modeling—Population Disease PK, exposure-response, and disease-state Models modeling are used to predict clinical outcomes, provide support for dose recommendations (justification and modification), assess safety and efficacy trends across exposure ranges, and inform “go/no go” decisions. CLINICAL PHARMACOLOGY TOOLS • PBPK—This technology informs key research As clinical and development (R&D) decisions relating to pharmacology has Using quantitative methods—among them, clinical trial design, first-in-human dosing, for- model-informed drug development (MIDD)—to mulation design, dosing in special populations, become increasingly optimize drug development decision-making is and predictions of the likelihood of drug-drug quantitative, it becoming core to the process. These methods, as interactions (DDIs). shown in Figure 2, are key components of clinical • Quantitative Systems Pharmacology (QSP)— has become more pharmacology and medical reviews. An emerging mechanistic modeling approach relevant and critical MIDD frequently provides answers to develop- focused on target exposure, binding, and ment gaps, increases understanding of benefit/risk, expression. It is employed to identify biological for decision-making identifies issues that need further characterization, pathways and disease determinants. QSP purposes. minimizes postmarketing burden, and informs helps understand PD as the disease progresses labeling decisions. Beyond the many ways that through the body. MIDD informs drug development decisions and • Quantitative Systems Toxicology (QST)—QST strengthens the science, it also reduces time and modeling combines toxicity and “omics” data to cost to market via smarter and potentially smaller focus on modes of action and adverse outcome or avoided studies. pathways. From FDA’s perspective, MIDD is a quantitative framework for using knowledge and inference generated from integrated models of compound-, THE RIGHT DRUG/PATIENT/DOSE/TIME mechanism-, and disease-level data to predict Clinical pharmacology, as the quarterback of and extrapolate how drug candidates should or drug development, plays a strategic role across will perform from pharmacokinetic/pharmacody- the entire process. As clinical pharmacology has namic (PK/PD), safety, and efficacy standpoints. become increasingly quantitative, it has become PK is what the body does to the drug (drug concen- more relevant and critical for decision-making tration); PD is what the drug does to the body (drug purposes. Figure 3 affirms the growing importance effect); PK/PD is the drug action over time. and impact of MIDD within the industry and its acceptance by global regulators. June 2017 22 Clinical Researcher Right Drug continues to grow, new methods, approaches, It is now largely understood that incorrect target tools, and technologies to expedite target selection selection and validation contribute to drug attrition. and validation are needed. Too often, drugs progress through the R&D process The aforementioned QSP, an emerging tool in with a poor understanding of the drug target or the clinical pharmacology, focuses on improving tar- appropriate mechanism of action for the targeted get selection and validation through mechanistic disease condition. A drug candidate may fail to modeling. QSP combines computational modeling interact with the target of interest in humans, and experimental data to examine the relation- or the drug may interact with the target without ships between a drug, the biological system, and benefitting the patient. Furthermore, a drug may not the disease process. This systems-level perspective affect a target’s downstream biochemical pathway integrates quantitative drug data with knowledge after target binding, or unforeseen safety problems of its mechanism of action. may emerge.3 Some believe that up to 40% of new QSP models can be used to address the complex projects closed for efficacy reasons were due to lack and heterogeneous diseases prevalent today. of data linking the target to the disease.4 Leveraging QSP can reduce Phase II attrition At the core of these failures are fundamental by allowing the investigation of a wide range of knowledge gaps regarding intended targets, their what-if scenarios to determine what the likely effi- biological relevance to a given disease, their cacy of the drug is going to be in advance of clinical interactions with the investigational compound, investigation. This can facilitate lead optimization or a compound’s therapeutic mechanism of action. very early on in the discovery process.5 As the sizeable list of potential disease targets FIGURE 3: Achieving the Right Drug/Dose/Time Using MIDD Preclinical Phase I Safety Phase II Efficacy Phase III Population Filing PK/PD PK/PD Safety In Vitro PD Biomarkers Biomarkers Efficacy Animal PK/PD Safety Safety PK Preliminary Efficacy Efficacy Data Generated Data PBPK, PK/PD QSP Integrated ER/DR ER/DR Preclinical PK/PD ER/DR Safety PopPk ER PopPk Efficacy Analysis Tools Go/No Go Data-driven dose Go/No Go Target Selection Phase III Dose modifications Regimen Feasibility Intrinsic Factors for safety Decisions Selection Extrinsic Factors and efficacy QSP: Quantitative Systems Pharmacology, ER: Exposure-response, DR: Dose-response, PopPK: Population PK Clinical Researcher 23 June 2017 Right Patient with various drug characteristics (e.g., DDIs, food We know that individuals react differently to interactions) to recommend when and how that identical therapeutics. In fact, drugs used today are individual receives the
Load more

Recommended publications
  • CPT Fellowship Psychopharm Focus
    Clinical Pharmacology and Toxicology Residency Program, McGill University One year Fellowship in Clinical Pharmacology and Toxicology: Psychopharmacology Focus Fellowship Director: Dr. Theodore Kolivakis, MD, FRCPC Program Director: Dr. Howard Margolese Location: MUHC (70-90%) JGH (10-20%) DH (10-20%) (% Depends on Selectives chosen based on interest of the Fellow) Number of Positions: 1 Length of Program: 1 year. The ‘academic’ year is July 1 to June 30, however ‘off-cycle’ candidates will also be considered Program General Information: The Clinical Pharmacology and Toxicology Fellowship: Psychopharmacology Focus is a one-year supervised training program open to qualified psychiatry residents who have completed their Psychiatry Postgraduate training and are eligible for practice in Canada. This fellowship program is based in the Clinical Psychopharmacology and Therapeutics Unit of the McGill University Health Centre (MUHC), Department of Psychiatry, McGill University, and is carried out in collaboration with a number of University hospitals and centers, namely the Clinical Toxicology Service of the MUHC, Alan Edwards Centre for Research on Pain at the MUHC, Internal Medicine at the MUHC or JGH (Hypertension clinic), Douglas Mental Health University Institute, and the Montreal Neurological Hospital and Institute; as well as the Department of Pharmacy of the MUHC. The objective of this program is to provide advanced training in clinical pharmacology and toxicology with a psychopharmacology focus to residents interested in gaining an expertise in the pharmacological treatment of their patients. Specifically they will learn best practices for 1. patients with complex medication regimes, 2. treatment resistant patients, 3. adverse drug reactions including iatrogenic ADR 4. consultation based care and practices After successfully completing the fellowship it is expected that fellows will become experts in the management of the most difficult psychiatric patients who are often those with significant other medical co-morbidities.
    [Show full text]
  • Clinical Pharmacology 1: Phase 1 Studies and Early Drug Development
    Clinical Pharmacology 1: Phase 1 Studies and Early Drug Development Gerlie Gieser, Ph.D. Office of Clinical Pharmacology, Div. IV Objectives • Outline the Phase 1 studies conducted to characterize the Clinical Pharmacology of a drug; describe important design elements of and the information gained from these studies. • List the Clinical Pharmacology characteristics of an Ideal Drug • Describe how the Clinical Pharmacology information from Phase 1 can help design Phase 2/3 trials • Discuss the timing of Clinical Pharmacology studies during drug development, and provide examples of how the information generated could impact the overall clinical development plan and product labeling. Phase 1 of Drug Development CLINICAL DEVELOPMENT RESEARCH PRE POST AND CLINICAL APPROVAL 1 DISCOVERY DEVELOPMENT 2 3 PHASE e e e s s s a a a h h h P P P Clinical Pharmacology Studies Initial IND (first in human) NDA/BLA SUBMISSION Phase 1 – studies designed mainly to investigate the safety/tolerability (if possible, identify MTD), pharmacokinetics and pharmacodynamics of an investigational drug in humans Clinical Pharmacology • Study of the Pharmacokinetics (PK) and Pharmacodynamics (PD) of the drug in humans – PK: what the body does to the drug (Absorption, Distribution, Metabolism, Excretion) – PD: what the drug does to the body • PK and PD profiles of the drug are influenced by physicochemical properties of the drug, product/formulation, administration route, patient’s intrinsic and extrinsic factors (e.g., organ dysfunction, diseases, concomitant medications,
    [Show full text]
  • IJBCP International Journal of Basic & Clinical Pharmacology Antibiotic
    Print ISSN: 2319-2003 | Online ISSN: 2279-0780 IJBCP International Journal of Basic & Clinical Pharmacology DOI: http://dx.doi.org/10.18203/2319-2003.ijbcp20191567 Original Research Article Antibiotic sensitivity profile and resistance of microorganisms isolated from south Indian population, a hospital based study at Velappanchavady, Chennai, India Brethis C. S.1*, Mahender G.2, Thamizharasan S.1, Suresh Kumar K.3, Sudharson T.3 1Department of Pharmacology, A.C.S Medical College and ABSTRACT Hospital, Velappanchavadi, Chennai, Tamil Nadu, India Background: Increasing rates of antibiotic drug resistance has been noted in 2Department of Forensic recent times and this adversely affects the prognosis and outcomes of patients. Medicine and Toxicology, There is a greater need for local resistance prevalence data in order to guide District Hospital Gajwel, empirical prescription and to identify areas in which medical need for newer Telangana, India antimicrobial agents is greater. 3Department of Forensic Methods: A prospective hospital based observational study was carried out to Medicine and Toxicology, determine antibiotic sensitivity profile and resistance pattern of microorganisms. A.C.S Medical College and Samples were collected from urinary tract infections, while cultures from blood Hospital, Velappanchavadi, stream infections, sputum samples and Serology. Antibiotic susceptibility was Chennai, Tamil Nadu, India determined by the standard disc diffusion method. Data interpretation was based on CLSI, 2017 guidelines for antimicrobial susceptibility testing. Received: 14 April 2019 Results: The predominant isolates from the samples were, Staphylococcus Accepted: 19 April 2019 aureus (16.7%) 67, K. pneumoniae (11.5%) 46, E. coli (29.4%) 118, P. aeruginosa (6%) 24. Escherichia coli, the most common causative organism *Correspondence to: showed high resistance to commonly used drugs such as Ampicillin (60.1%) 71, Dr.
    [Show full text]
  • Clinical Pharmacology and Pharmacogenomics Fellowship Research Training
    CCPP COMMITTEE ON CLINICAL PHARMACOLOGY AND PHARMACOGENOMICS Clinical Pharmacology and Pharmacogenomics Fellowship Research Training The Committee on Clinical Pharmacology and Pharmacogenomics at the University of Chicago, chaired by M. Eileen Dolan, PhD, is seeking motivated trainees for our clinical pharmacology and pharmacogenomics fellowship training program. Candidates should have a PhD, MD, PharmD/PhD or PharmD degree and have successfully completed a clinical residency. Ability to demonstrate a commitment to research, including but not limited to evidence provided by a record of prior publication is encouraged. This program is open to those interested in personalized medicine, pharmacogenomics, new drug development, clinical pharmacology, clinical trial design, genome wide association studies, genetics of drug abuse and/or overcoming drug resistance. Our two-year American Board of Clinical Pharmacology (ABCP) accredited program is a multidisciplinary, comprehensive and collaborative initiative that emphasizes individual creativity in the context of an encouraging environment. The two-year fellowship provides salary support/benefits for protected research time dedicated to research efforts along with support to attend meetings. Trainees will have the opportunity to tailor their work to emphasize clinical, translational or basic science research spending protected time devoted to their research efforts with the remainder dedicated to core curriculum and clinical activities (as applicable). After successful completion, trainees are eligible to become board certified in Clinical Pharmacology. General information at: http://ccpp.uchicago.edu/ or contact the programs’ educational manager, Michelle Domecki at [email protected]. Candidates who are U.S. citizens or permanent residents will be considered for support via an institutional training grant. The University of Chicago is an Equal Opportunity/Affirmative Action Employer.
    [Show full text]
  • Bioavailability and Bioequivalence Studies Submitted in Ndas Or Inds — General Considerations
    Guidance for Industry Bioavailability and Bioequivalence Studies Submitted in NDAs or INDs — General Considerations DRAFT GUIDANCE This guidance document is being distributed for comment purposes only. Comments and suggestions regarding this draft document should be submitted within 60 days of publication in the Federal Register of the notice announcing the availability of the draft guidance. Submit electronic comments to http://www.regulations.gov. Submit written comments to the Division of Dockets Management (HFA-305), Food and Drug Administration, 5630 Fishers Lane, rm. 1061, Rockville, MD 20852. All comments should be identified with the docket number listed in the notice of availability that publishes in the Federal Register. For questions regarding this draft document contact the CDER Office of Clinical Pharmacology at 301-796-5008 or [email protected]. U.S. Department of Health and Human Services Food and Drug Administration Center for Drug Evaluation and Research (CDER) March 2014 Biopharmaceutics Guidance for Industry Bioavailability and Bioequivalence Studies Submitted in NDAs or INDs— General Considerations Additional copies are available from: Office of Communications Division of Drug Information, WO51, Room 2201 Center for Drug Evaluation and Research Food and Drug Administration 10903 New Hampshire Avenue, Silver Spring, MD 20993 http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/default.htm Phone: 301-796-3400; Fax: 301-847-8714 [email protected] U.S. Department of Health and Human Services Food
    [Show full text]
  • BIOEQUIVALENCE and STATISTICS in CLINICAL PHARMACOLOGY
    Interdisciplinary Statistics BIOEQUIVALENCE and STATISTICS in CLINICAL PHARMACOLOGY Scott Patterson GlaxoSmithKline Pharmaceuticals Pennsylvania, USA Byron Jones Pfizer Global Research & Development Kent, UK Chapman & Hall/CRC Taylor & Francis Croup Boca Raton London New York Contents Preface xi List of figures xiii List of tables xv 1 Drug Development and Clinical Pharmacology 1 1.1 Aims of This Book 2 1.2 Drug Development 3 1.3 Clinical Pharmacology 5 1.4 Statistics in Clinical Pharmacology 11 1.5 Structure of the Book 14 2 History and Regulation of Bioequivalence 17 2.1 When and How BE Studies Are Performed 19 2.2 Why Are BE Studies Performed? 27 2.3 Deciding When Formulations Are Bioequivalent 28 2.4 Potential Issues with TOST Bioequivalence 32 2.5 Current International Regulation 36 3 Testing for Average Bioequivalence 39 3.1 Background 39 3.2 Linear Model for 2 x 2 Data 44 3.3 Applying the TOST Procedure 49 3.4 Carry-over, Sequence, and Interaction Effects 52 3.5 Checking Assumptions Made about the Linear Model 56 3.6 Power and Sample Size for ABE in the 2x2 Design 58 3.7 Example Where Test and Reference Are Not ABE (il 3.8 Nonparametric Analysis 68 3.9 Some Practical Issues 76 4 BE Studies with More Than Two Periods 79 4.1 Background 80 4.2 Three-period Designs 81 viii CONTENTS 4.3 Within-subject Variability 87 4.4 Robust Analyses for Three Period Designs 90 4.5 Four-period Designs 92 4.6 Designs with More Than Two Treatments 96 4.7 Nonparametric Analyses of Tmax 102 4.8 Technical Appendix: Efficiency 116 4.9 Tables of Data 120
    [Show full text]
  • Action and Resistance Mechanisms of Antibiotics: a Guide for Clinicians
    J Anaesthesiol Clin Pharmacol. 2017 Jul-Sep; 33(3): 300–305. PMCID: PMC5672523 doi: 10.4103/joacp.JOACP_349_15: 10.4103/joacp.JOACP_349_15 PMID: 29109626 Action and resistance mechanisms of antibiotics: A guide for clinicians Garima Kapoor, Saurabh Saigal,1 and Ashok Elongavan2 Department of Microbiology, Gandhi Medical College, Bhopal, Madhya Pradesh, India 1Department of Trauma and Emergency, AIIMS, Bhopal, Madhya Pradesh, India 2Department of Critical Care Medicine, Columbia Asia Hospital, Bengaluru, Karnataka, India Address for correspondence: Dr. Garima Kapoor, Department of Microbiology, Gandhi Medical College, Bhopal, Madhya Pradesh, India. E-mail: [email protected] Copyright : © 2017 Journal of Anaesthesiology Clinical Pharmacology This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 3.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as the author is credited and the new creations are licensed under the identical terms. Abstract Infections account for a major cause of death throughout the developing world. This is mainly due to the emergence of newer infectious agents and more specifically due to the appearance of antimicrobial resistance. With time, the bacteria have become smarter and along with it, massive imprudent usage of antibiotics in clinical practice has resulted in resistance of bacteria to antimicrobial agents. The antimicrobial resistance is recognized as a major problem in the treatment of microbial infections. The biochemical resistance mechanisms used by bacteria include the following: antibiotic inactivation, target modification, altered permeability, and “bypass” of metabolic pathway. Determination of bacterial resistance to antibiotics of all classes (phenotypes) and mutations that are responsible for bacterial resistance to antibiotics (genetic analysis) are helpful.
    [Show full text]
  • A Live Cell Nanobret Binding Assay Allows the Study of Ligand-Binding Kinetics to the Adenosine A3 Receptor
    Purinergic Signalling https://doi.org/10.1007/s11302-019-09650-9 ORIGINAL ARTICLE A live cell NanoBRET binding assay allows the study of ligand-binding kinetics to the adenosine A3 receptor Monica Bouzo-Lorenzo1,2 & Leigh A. Stoddart 1,2 & Lizi Xia3 & Adriaan P. IJzerman3 & Laura H. Heitman 3 & Stephen J. Briddon1,2 & Stephen J. Hill1,2 Received: 25 November 2018 /Accepted: 14 February 2019 # The Author(s) 2019 Abstract There is a growing interest in understanding the binding kinetics of compounds that bind to G protein-coupled receptors prior to progressing a lead compound into clinical trials. The widely expressed adenosine A3 receptor (A3AR) has been implicated in a range of diseases including immune conditions, and compounds that aim to selectively target this receptor are currently under development for arthritis. Kinetic studies at the A3AR have been performed using a radiolabelled antagonist, but due to the kinetics of this probe, they have been carried out at 10 °C in membrane preparations. In this study, we have developed a live cell NanoBRET ligand binding assay using fluorescent A3AR antagonists to measure kinetic parameters of labelled and unlabelled compounds at the A3AR at physiological temperatures. The kinetic profiles of four fluorescent antagonists were determined in kinetic association assays, and it was found that XAC-ser-tyr-X-BY630 had the longest residence time (RT = 288 ± 62 min) at the A3AR. The association and dissociation rate constants of three antagonists PSB-11, compound 5, and LUF7565 were also determined using two fluorescent ligands (XAC-ser- tyr-X-BY630 or AV039, RT = 6.8 ± 0.8 min) as the labelled probe and compared to those obtained using a radiolabelled antagonist ([3H]PSB-11, RT = 44.6 ± 3.9 min).
    [Show full text]
  • International Union of Basic and Clinical Pharmacology. XCVIII. Histamine Receptors
    1521-0081/67/3/601–655$25.00 http://dx.doi.org/10.1124/pr.114.010249 PHARMACOLOGICAL REVIEWS Pharmacol Rev 67:601–655, July 2015 Copyright © 2015 by The American Society for Pharmacology and Experimental Therapeutics ASSOCIATE EDITOR: ELIOT H. OHLSTEIN International Union of Basic and Clinical Pharmacology. XCVIII. Histamine Receptors Pertti Panula, Paul L. Chazot, Marlon Cowart, Ralf Gutzmer, Rob Leurs, Wai L. S. Liu, Holger Stark, Robin L. Thurmond, and Helmut L. Haas Department of Anatomy, and Neuroscience Center, University of Helsinki, Finland (P.P.); School of Biological and Biomedical Sciences, University of Durham, United Kingdom (P.L.C.); AbbVie, Inc. North Chicago, Illinois (M.C.); Department of Dermatology and Allergy, Hannover Medical School, Hannover, Germany (R.G.); Department of Medicinal Chemistry, Amsterdam Institute of Molecules, Medicines and Systems, VU University Amsterdam, The Netherlands (R.L.); Ziarco Pharma Limited, Canterbury, United Kingdom (W.L.S.L.); Institute of Pharmaceutical and Medical Chemistry (H.S.) and Institute of Neurophysiology, Medical Faculty (H.L.H.), Heinrich-Heine-University Duesseldorf, Germany; and Janssen Research & Development, LLC, San Diego, California (R.L.T.) Abstract ....................................................................................602 Downloaded from I. Introduction and Historical Perspective .....................................................602 II. Histamine H1 Receptor . ..................................................................604 A. Receptor Structure
    [Show full text]
  • Principles of Clinical Pharmacology Research
    1 Principles of Clinical Pharmacology Research PHAR 5230 Principles of Clinical Pharmacology Research 2 Credits Fall Semester 2019 Location/Time: WDH 7-193/Life Sci 160; Mondays 10:10 – 12:05 pm Course Delivery Director: Mark Kirstein, Pharm.D. Associate Professor Experimental and Clinical Pharmacology 717 Delaware Room 459 Phone : 612-624-5689 E-mail : [email protected] Participating Faculty: Swayam Prabha, Ph.D., M.S., MBA L’Aurelle Johnson, Ph.D. Assistant Professor Assistant Professor Experimental and Clinical Pharmacology Experimental and Clinical Pharmacology Phone: 612-626-3545- 7-115C Weaver-Densford Hall Email: [email protected] Phone: 612-624-5430 Fax: 612-625-3927 Email: [email protected] Jeff Bishop, Pharm.D. Ling Li, Ph.D. Associate Professor Professor and VFW Endowed Chair Experimental and Clinical Pharmacology Experimental and Clinical Pharmacology 14-271 Moos T 4-208 MTRF Phone : 612-625-5435 Phone: 612-626-2359 Email : [email protected] Email: [email protected] Scott Chapman, Pharm.D. Debra Skaar, Pharm.D. Associate Professor Associate Professor Experimental and Clinical Pharmacology Experimental and Clinical Pharmacology 7-115E Weaver-Densford Hall 7-109 Weaver-Densford Hall [email protected] Phone: 612-626-3005 E-mail: [email protected] Ramaiah Muthyala, Ph.D., FRSC Mahmoud Al Kofahi, D.D.S., Ph.D. Research Associate Professor Assistant Professor Experimental & Clinical Pharmacology717 Experimental and Clinical Pharmacology Delaware Rm 519University of Minnesota 717 Delaware Room 464 Minneapolis, MN Phone : 612-624-1161 [email protected] Email : [email protected] Pamala Jacobson, Pharm.D. Wendy St Peter, Pharm.D. Professor Professor Experimental and Clinical Pharmacology Pharmaceutical Care and Health Systems 7-151 Weaver-Densford Hall 7-176 Weaver-Densford Hall Phone:612-624-6118 Phone: 612-625-5848 Email: [email protected] Email: [email protected] 2 Michael Walters, Ph.D.
    [Show full text]
  • International Union of Pharmacology Committee on Receptor Nomenclature and Drug Classification
    0031-6997/03/5504-597–606$7.00 PHARMACOLOGICAL REVIEWS Vol. 55, No. 4 Copyright © 2003 by The American Society for Pharmacology and Experimental Therapeutics 30404/1114803 Pharmacol Rev 55:597–606, 2003 Printed in U.S.A International Union of Pharmacology Committee on Receptor Nomenclature and Drug Classification. XXXVIII. Update on Terms and Symbols in Quantitative Pharmacology RICHARD R. NEUBIG, MICHAEL SPEDDING, TERRY KENAKIN, AND ARTHUR CHRISTOPOULOS Department of Pharmacology, University of Michigan, Ann Arbor, Michigan (R.R.N.); Institute de Recherches Internationales Servier, Neuilly sur Seine, France (M.S.); Systems Research, GlaxoSmithKline Research and Development, Research Triangle Park, North Carolina (T.K.); and Department of Pharmacology, University of Melbourne, Parkville, Australia (A.C.) Abstract ............................................................................... 597 I. Introduction............................................................................ 597 II. Working definition of a receptor .......................................................... 598 III. Use of drugs in definition of receptors or of signaling pathways ............................. 598 A. The expression of amount of drug: concentration and dose ............................... 598 1. Concentration..................................................................... 598 2. Dose. ............................................................................ 598 B. General terms used to describe drug action ...........................................
    [Show full text]
  • Clinical Pharmacokinetics, 6Th Edition
    JOHN E. MURPHY, PharmD, FASHP, FCCP Professor of Pharmacy Practice and Science and Associate Dean, College of Pharmacy Professor of Clinical, Family and Community Medicine College of Medicine The University of Arizona Tucson, Arizona Honorary Professor The University of Otago School of Pharmacy Dunedin, New Zealand Any correspondence regarding this publication should be sent to the publisher, American Society of Health-System Pharmacists, 4500 East-West Highway, Suite 900, Bethesda, MD 20814, attention: Special Publishing. The information presented herein reflects the opinions of the contributors and advisors. It should not be interpreted as an official policy of ASHP or as an endorsement of any product. Because of ongoing research and improvements in technology, the information and its applications contained in this text are constantly evolving and are subject to the professional judgment and interpretation of the practitioner due to the uniqueness of a clinical situation. The editors and ASHP have made reasonable efforts to ensure the accuracy and appropriateness of the information presented in this document. However, any user of this information is advised that the editors and ASHP are not responsible for the continued currency of the information, for any errors or omissions, and/or for any consequences arising from the use of the information in the document in any and all practice settings. Any reader of this document is cautioned that ASHP makes no representation, guarantee, or warranty, express or implied, as to the accuracy and appropriateness of the information contained in this document and specifically disclaims any liability to any party for the accuracy and/or completeness of the material or for any damages arising out of the use or non-use of any of the information contained in this document.
    [Show full text]