This volume is a self-instructional computer-assisted medium for active learning. Indeed, the tutorial materials included in the accompanying compact disk have received an award from the American Association of Colleges of Pharmacy for innovation in teaching. This volume and its companion CD are intended for students and practitioners in the health professions who need to comprehend the concepts and principles related to how the body absorbs, distributes, metabolizes, and excretes drugs. "!The author's reliance on active learning, his use of examples illustrating important pharmacokinetic principles, and particularly the thoughtful simulation tools he has developed make this text and its companion CD an extremely effective and enjoyable introduction to the field of pharmacokinetics." From the Foreword, Ronald J. Sawchuk Minneapolis, Minnesota Pharmacokinetics has become an essential component of all the processes involved in drug development, discovery, and preclinical evaluation, as well as with the clinical use of drugs. While this has led to the development of many highly complex techniques, basic pharmacokinetic concepts remain the backbone of all these new developments. Consequently, a thorough understanding of the basic concepts is essential before one can tackle the more involved and applied areas of pharmacokinetics. Basic Pharmacokinetics consists of two parts: textual printed materials and highly interactive computer-based presentations. Together, these provide a useful combination that makes it easy to grasp basic principles. The computer-based information is presented in a self-instructional format, which introduces concepts, utilizing highly interactive graphical presentations and simulations. It visualizes the interplay between the different pharmacokinetic parameters, observing how the change in one or more of these parameters impacts the drug concentration-time profile in the body. Uniquely and carefully designed, the learning modules in the CD closely support and complement the text, providing the learner with an opportunity to reinforce his or her understanding of the principles presented.

Table of Contents:
INTRODUCTION TO BIOPHARMACEUTICS AND PHARMACOKINETICS Application of the Biopharmaceutic and Pharmacokinetic Principles in the Biomedical Fields Pharmacokinetic Modeling Pharmacokinetic Simulation DRUG PHARMACOKINETICS FOLLOWING SINGLE INTRAVENOUS ADMINISTRATION The Elimination Rate Constant The Volume of Distribution The Half-life The Total Body Clearance The Area under the Curve Factors Affecting the Drug Blood Concentration-time Profile after a Single IV Bolus Dose DRUG ABSORPTION FOLLOWING ORAL ADMINISTRATION: BIOPHARMACEUTICAL CONSIDERATIONS Physiological Factors Affecting Oral Drug Absorption Physical Factors Affecting Oral Drug Absorption The Dosage Form Characteristics DRUG PHARMACOKINETICS FOLLOWING SINGLE ORAL DRUG ADMINISTRATION: THE RATE OF DRUG ABSORPTION Drug Absorption after Oral Administration The Plasma Concentration-Time Profile after a Single Oral Dose Determination of the Absorption Rate Constant Clinical Importance of the Absorption Rate Constant DRUG PHARMACOKINETICS FOLLOWING SINGLE ORAL DRUG ADMINISTRATION: THE EXTENT OF DRUG ABSORPTION The Purpose of the Bioavailability and Bioequivalence Studies Causes for Variation in Drug Bioavailability Pharmacokinetic Basis of Drug Bioavailability and Bioequivalence Determination of the Drug Bioavailability Regulatory Requirements for Bioavailability and Bioequivalency Factors Affecting the Blood Concentration-time Profile after a Single Oral Dose THE STEADY-STATE PRINCIPLE AND DRUG PHARMACOKINETICS DURING CONSTANT-RATE INTRAVENOUS INFUSION The Plasma Concentration during Continuous Constant-Rate IV Drug Administration The Time Required to Reach Steady-State Loading Dose Determination of the Pharmacokinetic Parameters Effect of Changing the Pharmacokinetic Parameters on the Steady-State Plasma Concentration during Constant-Rate IV Infusion STEADY-STATE DURING MULTIPLE DRUG ADMINISTRATIONS The Drug Plasma Concentration-time Profile during Multiple Drug Administrations Average Plasma Concentration at Steady-State The Time Required to Reach Steady-State Loading Dose Drug Accumulation Controlled-release Formulations Effect of Changing the Pharmacokinetic Parameters on the Steady-State Plasma Concentration during Repeated Drug Administration Dosage Regimen Design RENAL DRUG ELIMINATION. Mechanisms of Renal Excretion of Drugs Determination of the Renal Excretion Rate The Renal Clearance The Cumulative Amount of the Drug Excreted in Urine Determination of the Pharmacokinetic Parameters from the Renal Excretion Rate Data Effect of Changing the Pharmacokinetic Parameters on the Urinary Excretion of Drugs METABOLITE PHARMACOKINETICS Simple Model for Metabolite Kinetics General Model for Metabolite Kinetics Estimation of the Metabolite Pharmacokinetic Parameters The Effect of Changing the Pharmacokinetic Parameters on the Drug and Metabolite Concentration-time Profiles after a Single IV Drug Administration Steady-State Metabolite Concentration during Repeated Administrations of the Parent Drug Effect of Changing the Pharmacokinetic Parameters on the Steady-State Drug and Metabolite Concentrations during Repeated Drug Administrations DISEASE STATE AND DRUG PHARMACOKINETICS Patients with Kidney Dysfunction Patients with Liver Diseases NONLINEAR PHARMACOKINETICS Michaelis-Menten Enzyme Kinetics Determination of the Pharmacokinetic Parameters Effect of Changing the Pharmacokinetic Parameters on the Plasma Concentration-time Profile Oral Administration of Drugs Eliminated by a Michaelis-Menten Process Pharmacokinetic Parameter Determination and Dosage Recommendation MULTICOMPARTMENT PHARMACOKINETIC MODELS The Two-Compartment Pharmacokinetic Model The Parameters of the Two-compartment Pharmacokinetic Model Determination of the Two-Compartment Pharmacokinetic Model Parameters Effect of Changing the Pharmacokinetic Parameters on the Drug Concentration-time Profile After a Single IV Dose Oral Administration of Drugs that Follow the Two-compartment Pharmacokinetic Model Constant Rate IV Administration of Drugs that Follow the Two-Compartment Pharmacokinetic Model Multiple Drug Administrations Renal Excretion of Drugs that Follow a Two-Compartment Pharmacokinetic Model Effect of Changing the Pharmacokinetic Parameters on the Drug Distribution between the Central and Peripheral Compartments The Three-Compartment Pharmacokinetic Model DRUG PHARMACOKINETICS FOLLOWING ADMINISTRATION BY INTERMITTENT INTRAVENOUS INFUSION The Drug Concentration-time Profile During Intermittent IV Infusion Effect of Changing the Pharmacokinetic Parameters on the Steady-State Plasma Concentration During Repeated Intermittent IV Infusion Application of the Pharmacokinetic Principles for Intermittent IV Infusion to the Therapeutic Use of Aminoglycoside Individualization of Aminoglycoside Therapy NONCOMPARTMENTAL APPROACH TO PHARMACOKINETIC DATA ANALYSIS The Noncompartmental Approach in Data Analysis The Mean Residence Time Other Pharmacokinetic Parameters that can be Determined Using the Noncompartmental Approach PHYSIOLOGICAL APPROACHTO HEPATIC CLEARANCE Organ Clearance Hepatic Extraction Ratio Intrinsic Clearance (CLint) Systemic Bioavailability The Effect of the Change in Intrinsic Clearance and Hepatic Blood Flow on the Hepatic Clearance, Systemic Availability, and Drug Concentration-time Profile Protein Binding and Hepatic Extraction PHARMACOKINETIC-PHARMACODYNAMIC RELATIONSHIP Pharmacodynamic Models The Link between the Pharmacokinetic and the Pharmacodynamic Models Application of Pharmacodynamic Models THERAPEUTIC DRUG MONITORING General Principles of Initiation and Management of Drug Therapy The Therapeutic Range The Variability in the Drug Pharmacokinetics and Response Advantages of Therapeutic Drug Monitoring Candidate Drugs for Therapeutic Drug Monitoring Methods for Measuring Drug Blood Concentrations Establishing a Therapeutic Drug Monitoring Service SOLUTIONS FOR THE PRACTICE PROBLEMS