Basic Pharmacokinetics and Pharmacodynamics
eBook - ePub

Basic Pharmacokinetics and Pharmacodynamics

An Integrated Textbook and Computer Simulations

Sara E. Rosenbaum, Sara E. Rosenbaum

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eBook - ePub

Basic Pharmacokinetics and Pharmacodynamics

An Integrated Textbook and Computer Simulations

Sara E. Rosenbaum, Sara E. Rosenbaum

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About This Book

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. ā€¢ Presents the essentials of pharmacokinetics and pharmacodynamics in a clear and progressive manner
ā€¢ 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
ā€¢ Features interactive computer simulations, available online through a companion website at: https://web.uri.edu/pharmacy/research/rosenbaum/sims/
ā€¢ 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
ā€¢ Reviews of the 1st edition: "This is an ideal textbook for those starting out ā€¦ and also for use as a reference book ā€¦." (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 ā€¦. " (British Toxicology Society Newsletter)

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Information

Publisher
Wiley
Year
2016
ISBN
9781119143185
Edition
2
Topic
Medizin

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 Concentrationā€“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 Doseā€“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 doseā€“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 inputā€“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.
images
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 ā€œdrug,ā€ pharmackon, and dynamics means ā€œof or relating to variation of intensity.ā€ 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 responseā€“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 Interac...

Table of contents

Citation styles for Basic Pharmacokinetics and Pharmacodynamics

APA 6 Citation

[author missing]. (2016). Basic Pharmacokinetics and Pharmacodynamics (2nd ed.). Wiley. Retrieved from https://www.perlego.com/book/994413/basic-pharmacokinetics-and-pharmacodynamics-an-integrated-textbook-and-computer-simulations-pdf (Original work published 2016)

Chicago Citation

[author missing]. (2016) 2016. Basic Pharmacokinetics and Pharmacodynamics. 2nd ed. Wiley. https://www.perlego.com/book/994413/basic-pharmacokinetics-and-pharmacodynamics-an-integrated-textbook-and-computer-simulations-pdf.

Harvard Citation

[author missing] (2016) Basic Pharmacokinetics and Pharmacodynamics. 2nd edn. Wiley. Available at: https://www.perlego.com/book/994413/basic-pharmacokinetics-and-pharmacodynamics-an-integrated-textbook-and-computer-simulations-pdf (Accessed: 14 October 2022).

MLA 7 Citation

[author missing]. Basic Pharmacokinetics and Pharmacodynamics. 2nd ed. Wiley, 2016. Web. 14 Oct. 2022.