Principles of Clinical Pharmacology临床药理学原理_精品.doc

PRINCIPLES OF CLINICAL PHARMACOLOGY Steven P. Stratton, Ph.D. Research Associate Professor of Medicine University of Arizona Address: Arizona Cancer Center 1515 N Campbell Ave PO Box 245024 Tucson, AZ 85724 (520) 626-9295 Running Title: Clinical Pharmacology Learning Objectives Define Pharmacokinetics Pharmacodynamics Identify pharmacokinetic/pharmacodynamic approaches, terminology, and parameters Recognize and develop endpoints for pharmacokinetic/pharmacodynamic modeling Identify barriers to molecularly targeted drug development Understand practical considerations in design of pharmacokinetic studies in clinical protocols Introduction to Pharmacokinetics and Pharmacodynamics Antineoplastic chemotherapeutic agents have the lowest therapeutic indices of commonly used classes of drugs1. The distinction between drug and poison is very small. Thus, pharmacologically rational approaches are crucial to avoiding disastrous outcomes. A drug is any pure chemical substance that alters a normal physiologic process when administered to an organism. To study how drugs work, pharmacologists have mystified the process by creating complex terms to describe relatively simple concepts. These terms include pharmacokinetics and pharmacodynamics. There are four possible outcomes following drug administration. These outcomes include: Efficacy without toxicity Efficacy with toxicity Toxicity without efficacy Neither toxicity nor efficacy Pharmacokinetic and pharmacodynamic modeling incorporated into clinical trial design can be used to optimize the best outcome for drug therapy2. Pharmacokinetics (PK) is the mathematical study of drug disposition (absorption, distribution, metabolism, and excretion). In trite terms, PK studies what the body does to the drug. Pharmacodynamics (PD) is the study of the dose-response relationship (the core principle of pharmacology), which is often represented as a Sigmoid Emax Model described by the Modified Hill Equation: E = (Emax