This book introduces basic pharmacokinetic concepts to beginner learners to help them understand the absorption, distribution, metabolism, and excretion of drugs. After a basic introduction to pharmacokinetics and its related fields, the book provides a clear introduction to quantitative pharmacokinetic relations and the interplay between pharmacokinetic parameters after different routes of drug administration. Emphasizing the application and importance of pharmacokinetic concepts in clinical practice throughout, the book features: A clear, simple, and concise style with the use of graphs and simulations to aid learning. Bullet point summaries of each concept to demonstrate applications in clinical practice. Practice problems and solved examples to help the reader understand the best approach for calculating pharmacokinetic parameters. A glossary of key words and acronyms. This book is an essential read for undergraduate and graduate pharmacokinetic students in pharmacy, pharmacology, and pharmaceutical science programs worldwide. Accompanying the book is a website with self-instructional tutorials and pharmacokinetic simulations, allowing visualization of concepts for enhanced comprehension. This learning tool received an award from the American Association of Colleges of Pharmacy for innovation in teaching, making it a valuable supplement to this textbook.

Drug metabolism/pharmacokinetics and drug interaction studies have been extensively carried out in order to secure the druggability and safety of new chemical entities throughout the development of new drugs. Recently, drug metabolism and transport by phase II drug metabolizing enzymes and drug transporters, respectively, as well as phase I drug metabolizing enzymes, have been studied. A combination of biochemical advances in the function and regulation of drug metabolizing enzymes and automated analytical technologies are revolutionizing drug metabolism research. There are also potential drug–drug interactions with co-administered drugs due to inhibition and/or induction of drug metabolic enzymes and drug transporters. In addition, drug interaction studies have been actively performed to develop substrate cocktails that do not interfere with each other and a simultaneous analytical method of substrate drugs and their metabolites using a tandem mass spectrometer. This Special Issue has the aim of highlighting current progress in drug metabolism/pharmacokinetics, drug interactions, and bioanalysis.

This book, Drug Metabolism and Pharmacokinetics, delivers the latest information on biotransformation and other pharmacokinetic parameters required to assess drug safety in drug discovery and development. Drug metabolism and pharmacokinetics (DMPK) is considered a rational strategy for the design, optimization, and selection of successful drug candidates in the pre-clinical stages of drug discovery. The evaluation of various pharmacokinetic parameters such as aqueous solubility, lipophilicity, cell permeability, bioavailability, protein binding, and metabolism and elimination half-life, drug–drug interactions (DDIs), and toxicokinetics is essential for a candidate drug to become a successful therapeutic agent. This book discusses recent advances in in-silico tools and in vitro/in vivo experimental techniques applied in pharmacokinetic, metabolomic, and bioanalytical studies. Key Features: • Presents pharmacokinetic and biotransformation parameters used for pre-clinical safety evaluations • Depicts experimental and biophysical techniques used in bioanalytical and metabolomic studies • Summarizes in silico, in vitro, and in vivo methods used in drug–enzyme interactions, drug– drug interactions, and toxicokinetics Written by a global team of experts, this book is a valuable resource for drug discovery scientists, drug developers, medicinal chemists, pharmacologists, biochemists, clinicians, biomedical scientists, healthcare professionals, researchers, teaching faculty, and students.

Clinically-focussed, with easily accessible tables and chapter summaries suitable for clinicians and researchers, this comprehensive book provides a systematic, critical evaluation of the current literature. An updated clinical decision-making algorithm specifically tailored to the antiretroviral drugs is also provided. The identified interactions are interpreted in the context of known mechanisms derived from clinical, preclinical, and in vitro data. The clinical relevance of the interactions is systematically evaluated and gaps in literature discussed in the context of potential future experiments. In addition to the comprehensive summary of pharmacokinetic and pharmacodynamic drug interactions associated with WHO-recommended antiretroviral drugs on the market today (i.e. nucleotide reverse-transcriptase inhibitors, non-nucleoside reverse-transcriptase inhibitors, integrase inhibitors, and protease inhibitors), this book also provides detailed section summaries on the epidemiology of HIV infection, diagnosis and pharmacotherapy, basic pharmacology of the individual antiretrovirals, pertinent pre-clinical and in vitro molecular pharmacology, and in vitro drug interaction data available in the literature today.

Knowledge of pharmacokinetics is critical to understanding the absorption, distribution, metabolism, and excretion of drugs. It is therefore vital to those engaged in the discovery, development, and preclinical and clinical evaluation of drugs, as well as practitioners involved in the clinical use of drugs. Using different approaches accessible to a wide variety of readers, Basic Pharmacokinetics: Second Edition demonstrates the quantitative pharmacokinetic relations and the interplay between pharmacokinetic parameters. After a basic introduction to pharmacokinetics and its related fields, the book examines: Mathematical operations commonly used in pharmacokinetics Drug distribution and clearance and how they affect the rate of drug elimination after a single dose Factors affecting drug absorption following extravascular drug administration, the rate and extent of drug absorption, and drug bioequivalence The steady-state concept during constant rate intravenous infusion and during multiple drug administration Renal drug elimination, drug metabolism, multicompartment models, nonlinear pharmacokinetics, and drug administration by intermittent intravenous infusion Pharmacokinetic-pharmacodynamic modeling, noncompartmental pharmacokinetic data analysis, clearance concept from the physiological point of view, and physiological modeling Clinical applications of pharmacokinetics, including therapeutic drug monitoring, drug pharmacokinetics in special populations, pharmacokinetic drug-drug interactions, pharmacogenomics, and applications of computers in pharmacokinetics Accompanying the book is a CD-ROM with self-instructional tutorials and pharmacokinetic and pharmacokinetic-pharmacodynamic simulations, allowing visualization of concepts for enhanced comprehension. This learning tool received an award from the American Association of Colleges of Pharmacy for innovation in teaching, making it a valuable supplement to this essential text.

Many aspects of drug safety have become an outstanding and even persistent issue and may occur during the process of both drug discovery and development. Until 15 years ago, drug discovery and evaluation was primarily a sequential process starting with the selection of the most pharmacologically active compound from a series of newly synthesized small molecule chemical series by means of distinctive pharmacological assays. Safety aspects were addressed by evaluation of the selected compound at high doses in a series of specific studies directed at indications other than the intended indication of the new compound. These tests are then followed by pharmacokinetic studies, which are primarily conducted to confirm whether the selected compound possesses a suitable half-life for sufficient exposure and efficacy and, whether it has the desired properties specificity to the intended route of administration. Safety aspects relied predominantly on the conduct of single and repeat toxicologydose studies, which inform changes in organ structure rather than organ function. Both toxicological and pharmacokinetic studies are adapted to the progress of studies in clinical pharmacology and clinical trials. The new edition of this well and broadly accepted reference work contains several innovative and distinguished chapters. This "sequential" strategy has been abandoned with this new version of the book for several reasons: - Of the possible multitude of negative effects that novel drugs may impart on organ function, e.g. ventricular tachy-arrhythmia, many are detected too late in non-clinical studies to inform clinicians. On the other hand, negative findings in chronic toxicity studies in animals may turn out to be irrelevant for human beings. - New scientific approaches, e.g. high-throughput screening, human pluripotent stem cells, transgenic animals, knock-out animals, in silico models, pharmaco-genomics and pharmaco-proteomics, as well as Artificial Intelligence (AI) methods offered new possibilities. - There are several examples, that show that the "druggability" of compounds was considerably underestimated when the probability of success of a new project was assessed. The success rate in the pharmaceutical industry and the introduction of new chemical entities to the market per year dropped dramatically, whereas the development time for a new compound increased, sometimes exceeding the patent protection. Research and development scientists, involving the following changes, therefore adopted a change of strategy: - Parallel instead of sequential involvement of the various disciplines (multidimensional compound optimization). - The term "Safety Pharmacology" was coined. The International Conference on Harmonization (ICH) founded a Safety Pharmacology Working Group and the Safety Pharmacology Society (SPS) was launched. The discipline provided for evaluation, development and validation of a multitude of safety tests outlined in the 'Core Battery of Studies'. - Characterizing the exposure profile of a drug by conducting pharmacokinetic studies that evaluates the absorption, distribution, metabolism and excretion should to be investigated at an early stage of development as results contribute to the selection of a compound for further development. Advancements in Toxicology were achieved by the introduction of new methods, e.g., in silico methods, genetic toxicology, computational toxicology and AI. The book is a landmark in the continuously changing world of drug research and developments. As such, it is essential reading for many groups: not only for all students of pharmacology and toxicology but also for industry scientists and physicians, especially those involved in clinical trials of drugs, and for pharmacists who must know the safety requirements of drugs. The book is essential for scientists and managers in the pharmaceutical industry who are involved in drug discovery, drug development and decision making in the development process. In particular, the book will be of use to government institutions and committees working on official guidelines for drug evaluation worldwide.

Drug Disposition and Pharmacokinetics The most up-to-date edition of a leading reference in drug disposition and pharmacokinetics In this new, fully-revised edition of Drug Disposition and Pharmacokinetics: Principles and Applications for Medicine, Toxicology and Biotechnology the authors deliver an authoritative and comprehensive discussion of the fate of drug molecules in the body, as well as its implications for pharmacological and clinical effects. The text offers a unique and balanced approach that combines discussion of the specific physical and biological factors affecting the absorption, distribution, metabolism, and excretion of drugs, with mathematical assessments of plasma and body fluid concentrations. The book assumes little prior knowledge and is an ideal reference for practicing professionals in industry as well as researchers and academics. This latest edition provides readers with a new introductory chapter, as well as new chapters covering monoclonal antibodies, the role of stereochemistry in drug disposition and pharmacokinetics, DMPK in non-human species, and the recent use of AI in drug development. Readers will also find: Thorough introductions to drug disposition, pharmacokinetics, and pharmacokinetic modeling In-depth treatments of the kinetics of drug elimination and the relationship between concentration and effect, including PK–PD modeling Comprehensive discussions of predictive pharmacokinetics and the disposition of biological molecules, including peptides and monoclonal antibodies Detailed examinations of the effects of sex, pregnancy, age, and disease, as well as drug monitoring in therapeutics and the use of AI in drug development and treatment Perfect for professionals and researchers working with the scientific aspects of drug disposition in human and veterinary medicine, toxicology, and pharmacology. Drug Disposition and Pharmacokinetics will earn a place in the libraries of students of senior-level courses in pharmacy.

This volume is an important advancement in the application ofpharmacokinetic (PK) and pharmacodynamic (PO) principles to . drug development. The series of topics presented deal with the application of these tools to everyday decisions that a pharmaceutical scientist encounters. The ability to integrate these topics using PK and PO methods has optimized drug development pathways in the clinic. New technologies in the areas of in vitro assays that are more predictive of human absorption and metabolism and advancement in bioanalytical assays are leading the way to minimize drug failures in later, more expensive clinical development programs. of Pharmacokinetics and pharmacodynamics have become an important component understanding the drug action on the body and is becoming increasingly important in drug labeling due to it's potential for predicting drug behavior in populations that may be difficult to study in adequate numbers during drug development. The ability to correlate drug exposure to effect and model it during the drug development value chain provides valuable insight into optimizing the next steps to derive maximum information from each study. These principles and modeling techniques have resulted in an expanded and integrated view of PK and PO and have led to the expectations that we may be able to optimally design clinical trials and eventually lead us to identifying the optimal therapy for the patient, while minimizing cost and speeding up drug development. There is wide utility for the book both as a text and as a reference.