Basic Pharmacokinetics and Pharmacodynamics (eBook)

An Integrated Textbook and Computer Simulations

Sara E. Rosenbaum (Herausgeber)

eBook Download: EPUB

2016 | 2. Auflage
Wiley (Verlag)
978-1-119-14318-5 (ISBN)

Infos

Updated with new chapters and topics, this book provides a comprehensive description of all essential topics in contemporary pharmacokinetics and pharmacodynamics. It also features interactive computer simulations for students to experiment and observe PK/PD models in action.
•    Presents the essentials of pharmacokinetics and pharmacodynamics in a clear and progressive manner
•    Helps students better appreciate important concepts and gain a greater understanding of the mechanism of action of drugs by reinforcing practical applications in both the book and the computer modules
•    Features interactive computer simulations, available online through a companion website at: https://web.uri.edu/pharmacy/research/rosenbaum/sims/
•    Adds new chapters on physiologically based pharmacokinetic models, predicting drug-drug interactions,  and pharmacogenetics while also strengthening original chapters to better prepare students for more advanced applications
•    Reviews of the 1st edition: 'This is an ideal textbook for those starting out ... and also for use as a reference book ....' (International Society for the Study of Xenobiotics) and 'I could recommend Rosenbaum's book for pharmacology students because it is written from  a perspective of drug action . . . Overall, this is a well-written introduction to PK/PD .... '  (British Toxicology Society Newsletter)

Sara E. Rosenbaum, PhD, is Professor of Biomedical and Pharmaceutical Sciences at the University of Rhode Island, where she teaches courses in pharmacokinetics and pharmacodynamics. Her research interests concentrate on the development and application of pharmacokinetic and pharmacodynamic models to better understand the drug dose-response relationship.

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Updated with new chapters and topics, this book provides a comprehensive description of all essential topics in contemporary pharmacokinetics and pharmacodynamics. It also features interactive computer simulations for students to experiment and observe PK/PD models in action. Presents the essentials of pharmacokinetics and pharmacodynamics in a clear and progressive manner Helps students better appreciate important concepts and gain a greater understanding of the mechanism of action of drugs by reinforcing practical applications in both the book and the computer modules Features interactive computer simulations, available online through a companion website at: https://web.uri.edu/pharmacy/research/rosenbaum/sims/ Adds new chapters on physiologically based pharmacokinetic models, predicting drug-drug interactions, and pharmacogenetics while also strengthening original chapters to better prepare students for more advanced applications Reviews of the 1st edition: This is an ideal textbook for those starting out and also for use as a reference book ."e; (International Society for the Study of Xenobiotics) and I could recommend Rosenbaum s book for pharmacology students because it is written from a perspective of drug action . . . Overall, this is a well-written introduction to PK/PD . (British Toxicology Society Newsletter)

Textauszug

CHAPTER 1
Introduction to Pharmacokinetics and Pharmacodynamics

SARA E. ROSENBAUM

1. 1.1 Introduction: Drugs and Doses
2. 1.2 Introduction to Pharmacodynamics
   1. 1.2.1 Drug Effects at the Site of Action
      1. 1.2.1.1 Interaction of a Drug with Its Receptor
      2. 1.2.1.2 Postreceptor Events
   2. 1.2.2 Agonists, Antagonists, and Concentration–Response Relationships
3. 1.3 Introduction to Pharmacokinetics
   1. 1.3.1 Plasma Concentration of Drugs
   2. 1.3.2 Processes in Pharmacokinetics
4. 1.4 Dose–Response Relationships
5. 1.5 Therapeutic Range
   1. 1.5.1 Determination of the Therapeutic Range
6. 1.6 Summary
7. Reference

Objectives

The material in this chapter will enable the reader to:

1. Define pharmacodynamics and pharmacokinetics
2. Understand the processes that control the dose–response relationship
3. Gain a general appreciation of how mathematical expressions in pharmacodynamics and pharmacokinetics can be used for the rational determination of optimum dosing regimens

1.1 Introduction: Drugs and Doses

Drugs may be defined as chemicals that alter physiological or biochemical processes in the body in a manner that makes them useful in the treatment, prevention, or cure of diseases. Based on this definition, any useful drug must affect body physiology or biochemistry. By extension, any useful drug must, if used inappropriately, possess the ability to do harm. Drug action begins with administration of the drug (input) and concludes with the biological response (output, which can be a beneficial and/or an adverse effect). The inputs (dose, frequency of administration, and route of administration) must be selected carefully to optimize the onset, intensity, and duration of therapeutic effects for a particular disease condition. At the same time, the inputs selected must minimize any harmful effects of drugs.

The design of optimum dosing regimens requires a complete understanding of the processes and steps that translate the input into the output. It also requires an understanding of how the input–output relationship may be influenced by individual patient characteristics that may exist at the very beginning of therapy, as well as conditions that may arise during the course of drug therapy. These will include the age and weight of the patient, the presence of other diseases, genetic factors, concurrent medications, and changes in the disease being treated over time.

The material presented in this book will address and explain why, as shown in Table 1.1, there is such tremendous variability in the value of drug doses and dosing frequencies among therapeutic drugs. Additionally, it will address why different routes of administration are used for different drugs and different indications (Table 1.1).

Table 1.1 Examples of Common Daily Doses and Dosing Intervals

Drug

Daily Dose (mg)

Dose Frequency (h)

Route

Calcium carbonate

3000

2

Oral

Ibuprofen

1600

6

Oral

Vancomycin (for MRSAa)

2000

12

Intravenous

Amoxicillin

750

8

Oral

Vancomycin (for pseudomembranous colitis)

1000

6

Oral

Atenolol

100

24

Oral

Fluoxetine

20

24

Oral

Ramipril

10

12

Oral

Digoxin

0.250

24

Oral

Chloroquine

300

Weekly

Oral

aMethicillin-resistant Staphylococcus aureus.

The steps between drug input and the emergence of the response can be broken down into two phases: pharmacokinetic and pharmacodynamic. The pharmacokinetic phase encompasses all the events between the administration of a dose and the achievement of drug concentrations throughout the body. The pharmacodynamic phase encompasses all the events between the arrival of the drug at its site of action and the onset, magnitude, and duration of the biological response (Figure 1.1). The rational design of optimum dosing regimens must be based on a thorough understanding of these two phases and will, ideally, include the development of one or more mathematical expressions for the relationship between dose and the time course of drug response.

Figure 1.1 The two phases of drug action. The pharmacokinetic phase is concerned with the relationship between the value of the dose administered and the value of the drug concentrations achieved in the body; the pharmacodynamic phase is concerned with the relationship between drug concentrations at the site of action and the onset, intensity, and duration of drug response.

Optimum drug administration is important not only for ensuring good patient outcomes in clinical practice, but also in the design of clinical trials during drug development. The cost of drug research and development is enormous, so it is critical that all drug candidates selected for human trials are evaluated in the most efficient, cost-effective manner possible.

The application of pharmacokinetic and pharmacodynamic principles to this process has been shown to enhance the selection of optimum doses and optimum designs of phase II clinical trials.

1.2 Introduction to Pharmacodynamics

Pharmaco- comes from the Greek word for “drug,” pharmackon, and dynamics means “of or relating to variation of intensity.” Pharmacodynamics (PD) is the study of the magnitude of drug response. In particular, it is the study of the onset, intensity, and duration of drug response and how these are related to the concentration of a drug at its site of action. An overview of some basic drug terminology and the drug response–concentration relationship is provided below.

1.2.1 Drug Effects at the Site of Action

Note that although some references and textbooks distinguish the terms drug effect and drug response, this distinction has not been adopted universally. In this book, effect and response are used interchangeably.

1.2.1.1 Interaction of a Drug with Its Receptor

Drug response is initiated by a chemical interaction between a drug and a special binding site on a macromolecule in a tissue. This macromolecule is known as a drug receptor. The drug–receptor interaction results in a conformational change in the receptor, which results in the generation of a stimulus that ultimately leads to a biochemical or physiological response (Figure 1.2). Most receptors (over 95%) are proteins; however, other types of receptors exist such as the DNA receptors of the alkylating agents used in cancer chemotherapy. The drug–receptor interaction involves chemical bonding, which is usually reversible in nature and can be expressed using the law of mass action (Figure 1.2). Thus, at the site of action, the drug binds to its receptor and equilibrium is established between the bound and the unbound drug. As the drug is eliminated from the body and removed from its site of action, it dissociates from the receptor, which is left unchanged, and the response dissipates.

Figure 1.2 Drug–receptor interaction. Here, AG signifies a drug agonist, [D] is the free drug concentration (not bound to the receptor), R is the concentration of free receptors, [RD] is the concentration of the drug–receptor complex, and kon and koff are the rate constants for the forward and backward processes, respectively.

In contrast, a few drugs form irreversible covalent bonds with their receptors. For example, aspirin inhibits platelet aggregation by inhibiting the formation of thromboxane in the platelets. It accomplishes this by binding covalently to and blocking the catalytic activity of cyclooxygenase, the enzyme that produces thromboxane. The effect of a single dose of aspirin will persist long after the drug has been removed from its site of action and will continue until new cyclooxygenase molecules are synthesized, which can then resume the production of thromboxane. Other examples of drugs that bind irreversibly to their receptors include the alkylating agents mentioned above and proton pump inhibitors, such as omeprazole, which block the secretion of gastric acid by binding irreversibly to the H+, K+-ATPase...

Produkt-Details

• Erscheint lt. Verlag: 28.11.2016
• Sprache: englisch
• Themenwelt: Medizin / Pharmazie ► Medizinische Fachgebiete ► Pharmakologie / Pharmakotherapie
• Themenwelt: Studium ► 2. Studienabschnitt (Klinik) ► Humangenetik
• Themenwelt: Naturwissenschaften ► Chemie
• Schlagworte: ADME • Bioavailability • Biopharmaceutics • Chemie • Chemistry • Clinical Pharmacology & Therapeutics • drug action mechanisms • drug administration • drug disintegration • Drug dissolution • Drug-drug Interactions • Klinische Pharmakologie u. Therapie • <p>PKPD • Medical Science • Medizin • Molecular Pharmacology • Molekulare Pharmakologie • non-compartmental analysis</p> • Pharmaceutical Statistics • Pharmacodynamics • Pharmacogenetics • Pharmacokinetics • Pharmakodynamik • Pharmakokinetik • Pharmakologie • Pharmazeutische Statistik • Physiologically Based Pharmacokinetic Modeling • PK/PD computer simulations • PK/PD models • predictive models for drug-drug interactions • Sara Rosenbaum • Statistics • Statistik • Transporters
• ISBN-10: 1-119-14318-7 / 1119143187
• ISBN-13: 978-1-119-14318-5 / 9781119143185