[...]... Preface to the Second Edition Five years have passed since the first edition of Principles of Clinical Pharmacology was published The second edition remains focused on the principles underlying the clinical use and contemporary development of pharmaceuticals However, recent advances in the areas of pharmacogenetics, membrane transport, and biotechnology and in our understanding of the pathways of drug metabolism,... subject of ancient interest but is a relatively new science Reidenberg (4) subsequently restated Leake’s listing of the fundamental problems with which the science of pharmacology is concerned: Optimizing Use of Existing Medicines 1 The relationship between dose and biological effect 2 The localization of the site of action of a drug 3 The mechanism(s) of action of a drug PRINCIPLES OF CLINICAL PHARMACOLOGY, ... currently are being applied in the process of drug development Journals Clinical Pharmacology and Therapeutics British Journal of Clinical Pharmacology Journal of Pharmaceutical Sciences Journal of Pharmacokinetics and Biopharmaceutics Web Sites American Society for Clinical Pharmacology and Therapeutics (ASCPT): http://www.ascpt.org/ The American Board of Clinical Pharmacology (ABCP): http://www.abcp.net/... discipline of clinical pharmacology (5) Their accomplishments include the invention of the double-blind design for clinical trials (6), the use of effect kinetics to measure the absolute bioavailability of digoxin and characterize the time course of its chronotropic effects (7), and the founding of Clinical Pharmacology and Therapeutics Few drugs have focused as much public attention on the problem of adverse... University of California, San Francisco; UC Washington Center Washington, DC 20036 Nicholas H.G Holford University of Auckland Department of Pharmacology and Clinical Pharmacology School of Medicine Grafton, Auckland New Zealand Lawrence J Lesko Food and Drug Administration Of ce of Clinical Pharmacology and Biopharmaceuticals, CDER Rockville, MD 20857 Sanford P Markey National Institute of Mental Health,... NY 10583 Sarah M Robertson NIH Clinical Center Pharmacy Department Bethesda, MD 20892 Paul Edward Rolan Department of Clinical and Experimental Pharmacology Medical School University of Adelaide SA 5005 Australia ICON - Medeval Clinical Pharmacology Manchester Science Park, Manchester United Kingdom Chandrahas G Sahajwalla Food and Drug Administration Of ce of Clinical Pharmacology and Biopharmaceuticals,... 33 Design of Clinical Development Programs CHARLES GRUDZINSKAS Introduction 501 Phases, Size, and Scope of Clinical Development Programs 501 Global Development 501 Clinical Drug Development Phases 502 Drug Development Time and Cost — A Changing Picture 502 Impact of Regulation on Clinical Development Programs 504 Goal and Objectives of Clinical Drug Development 505 Objective 1 — Clinical Pharmacology. .. problems in pharmacology can only be studied in humans This text will focus on the basic principles of clinical pharmacology Selected applications will be used to illustrate these principles, but no attempt will be made to provide an exhaustive coverage of applied therapeutics Other useful supplementary sources of information are listed at the end of this chapter Leake (3) has pointed out that pharmacology. .. to children 1 year of age: Children 1–13 years of age: Females 13–20 years of age: Males 13–20 years of age: k = 0.45 k = 0.55 k = 0.57 k = 0.70 From the standpoint of clinical pharmacology, the utility of using the Cockcroft and Gault equation, or other methods, to estimate creatinine clearance stems from the fact that these estimates can alert healthcare workers to the presence of impaired renal function... patients Dose-Related Toxicity Often Occurs When Impaired Renal Function is Unrecognized Failure to appreciate that a patient has impaired renal function is a frequent cause of dose-related 6 Principles of Clinical Pharmacology TABLE 1.1 Status of Renal Function in 44 Patients with Digoxin Toxicitya No of patients with CLCR of Serum creatinine 50 mL/min 1.7 . h1" alt="" PRINCIPLES OF CLINICAL PHARMACOLOGY Second Edition This page intentionally left blank PRINCIPLES OF CLINICAL PHARMACOLOGY Second Edition Arthur. http://www.cc.nih.gov/ccc /principles Preface to the Second Edition Five years have passed since the first edition of Principles of Clinical Pharmacology was published. The second