This comprehensive ebook covers all the aspects of ADME/PK modeling including solubility, absorption, formulation, metabolic stability, drug-drug interaction potential and a special delivery tool of drug candidates. The book provides an integrated view of fundamental ADME issues and challenges in early drug development from the aspect of practicing drug researchers. It also provides valuable help for the medicinal chemist in the process of multiple optimization.

Thermodynamics and kinetics (i.e., chemical interactions) are extremely important concepts for pharmaceutical scientists to understand since the “drug selection process”, that is, the process used by pharmaceutical companies to discover and develop marketable drugs, is totally dependent upon these theories. While both theories are important, kinetic models describing complex chemical and biological processes provide a unifying theory for all phases of the discovery and development of drugs. Unfortunately, in most textbooks the mathematical descriptions necessary to develop a deeper understanding of kinetic models are omitted. This is primarily done such that the underlying chemistry and biochemistry principles are not obscured by the “mathematical maze” that is generated from these models. As a result many chemists and biologists veer rapidly away from thermodynamics and kinetics. For some scientists, this can lead to confusion on how to apply these models to real-life situations. For example, many enzyme kinetic models are formulated as rate equations. Since experimentally measurements typically determine concentrations and rarely determines rates directly, confusion arises on how to apply kinetic models. In this case, either the model is integrated to give a description of the concentration course of the enzyme reaction or the data is differentiated (i.e., the process of determining rates) by measuring tangents to the reaction curves at zero time. The level of mathematical skills required to solve kinetic models is minimal for anyone who has studied college level algebra and calculus. Thus, the objective of this book is to present a brief review of thermodynamics and kinetics followed by a detailed step-by-step approach in developing and solving kinetic models for complex chemical and biological processes. The book focuses on building a solid mathematical foundation of enzyme kinetic models by systematically evolving simple uni- and bi-molecular models to enzyme models. Applications for some of these kinetic models are generated from pharmaceutical examples and a selection of problems is presented at the end of each chapter. This elementary approach has been intentionally selected to keep the book at a self-explanatory level. It is anticipated that the reader will be able to follow the mathematical operations and in the process develop a deeper understanding of kinetic models and an improved ability to interpret kinetic parameters. The book is restricted to solution chemical kinetics and does not deal with the theories of chemical reactions, gas-phase reactions, experimental kinetic methods and so on. There are many excellent chemical kinetic textbooks available for those interested in these topics. The solution chemical kinetics materials for the book were obtained from literature papers and several books on physical chemistry and enzyme kinetics. The ideas from these sources have been hopefully reinterpreted in a style that is well matched to those pharmaceutical scientists that do not have a comprehensive knowledge of kinetic models and the mathematical skills to solve them. Chapter 1 presents a general overview to thermodynamic and kinetic principals and theory. In Section i, an overview to the scope of the book is presented. A brief review of mathematical fundamentals used in the book (Section ii) and kinetic and thermodynamic principals are present (Section iii and iv). A glossary of symbols and abbreviation used throughout the book is presented in Section v. Chapter 2 describes the basic theory of first-order kinetic models. These types of mathematical models are used for irreversible (Section I) and reversible (Section II) rearrangement reactions and some examples are presented to illustrate their applications to drug discovery. Chapter 3 describes second-order irreversible (Section III) and reversible (Section IV) dimerization reactions while Chapter 4 describes second-order irreversible (Section V) and reversible (Section VI) binding reactions. Chapter 5 describes partially and fully coupled reversible completive binding reactions (Section VII). Chapter 6 describes second-order kinetic models that are used to analyze consecutive irreversible (Section VIII) and reversible (Section IX) substrate suicide enzyme reactions. Chapter 7 describes kinetic models that are used to analyze consecutive irreversible (Section X) and reversible (Sections XI and XII) enzyme reactions. Chapter 8 describes kinetic models that are used to analyze consecutive reversible inhibition enzyme reactions (Section XIII - XVI). Chapter 9 describes kinetic models that are used to analyze substrate (Section XVII) and product inhibition (Section XVIII) enzyme reactions. The Appendix contains the answers to the problems.

The endocannabinoid system comprises at least two G-protein-coupled receptors (the cannabinoid CB1 and CB2 receptors) activated by marijuana’s psychoactive principle ∆9-tetrahydrocannabinol (THC) and the endogenous ligands known as endocannabinoids. The apex of endocannabinoid research seems to have been reached with the clinical development, and also in some cases, the marketing, of synthetic or natural pharmaceuticals targeting this signalling system, which followed the understanding of the physiological and pathological role of endocannabinoids in several conditions, a role that was investigated first in rodent experimental models and then in humans. </p><p> Endocannabinoids: Molecular, Pharmacological, Behavioral and Clinical Features is a monograph that presents interesting manuscripts selected by the editor on the subject. Chapters in this book include original research or reviews which report the relevance of the endocannabinoid system by describing the results of experimental evidence about the neurobiological role of the endocannabinoid system. The main topics include, but are not limited to: </p><p> *The genetics of cannabinoid CB1 and CB2 receptors and their tissue distribution, their splicing variants and polymorphisms, and the possible implications of all this in determining different behaviours as well as various pathological conditions and the addiction to substances of abuse. </p><p> *Pharmacological approaches describing the potential use in the central nervous system disorders of endocannabinoid-based drugs, such as cannabinoid receptor agonists and antagonists, inhibitors of endocannabinoid inactivation processes, and even plant cannabinoids other than THC and with a molecular mechanism of action. </p><p> *The role of the endocannabinoid system in several neurological and neuropsychiatric conditions, such as epilepsy. </p><p> The volume would be a great interest to neuropharmacologists, physiologists and biochemists who aim to learn about the endocannabinoid system in detail.

Pharmaceutical manufacturing can be viewed as a supply chain which spans from the production and purchase of the starting and packaging materials through the manufacture of dosage forms until the safe reception of the finished product by the patient. The entire chain comprises of several processes: auditing, materials purchase (procurement), production, storage, distribution, quality control, and quality assurance. The quality standard for pharmaceutical production is ‘current good manufacturing practice (CGMP)’‘, which is applied within the frame of a pharmaceutical quality system (PQS). This implementation, however, requires a scientific approach and has to take into account several elements such as risk assessment, life cycle, patient protection, among other factors. Hence, pharmaceutical manufacturing is a complex subject in terms of regulation, given the technical and managerial requirements. This comprehensive handbook describes CGMP for new professionals who want to understand and apply the elements which build up pharmaceutical quality assurance. The book gives details about basic quality control requirements (such as risk management, quality hazards and management systems, documentation, clean environments, personnel training) and gives guidelines on regulatory aspects. This is an ideal handbook for undergraduates studying pharmaceutical or industrial manufacturing and supply chains as well for entrepreneurs and quality control professionals seeking to learn about CGMP standards and implementing quality assurance systems in the pharmaceutical sector.

Natural products continue to play a key role in drug development. A recent analysis of the drug market in the developed world revealed that 40% of total clinically approved drugs were either unmodified natural products or their semi-synthetic derivatives. This book series focuses on reviews of exciting new bioactive natural products that have huge potential as drugs. It highlights the everlasting importance of natural products in our lives. Each volume brings reviews contributed by eminent scientists in the field. The first volume covers the following topics: - bioactive compounds from marine invertebrates - natural product derived drugs for immunological and inflammatory diseases - clinical trials of curcumin, camptothecin, astaxanthin, and biochanin - antibacterial and antifungal drugs from natural sources - natural products as anti-HIV medicines

Natural compounds continue to play a key role in drug development. Many clinically approved drugs are either unmodified natural products or their semi-synthetic derivatives. This book series presents reviews of exciting new bioactive natural products that have huge potential as drugs. Each volume presents comprehensive chapters contributed by eminent scientists. The volumes focus on drug candidates which are in the later stages of drug development and are being evaluated in clinical trials. The series, therefore, highlights the importance of natural products in our lives. The second volume covers the following topics: - A review of recent patents and natural products in clinical trials to treat schistosomiasis - Natural products: the new intervention regimen for metabolic disorders - Fluorine-containing drugs and drug candidates derived from natural products - Natural products for the management of cardiovascular diseases - Implication of natural compounds for the prevention of ocular diseases

Natural bioactive compounds from medicinal plants are inexplicably diverse in chemical structure and biological properties. The unmet therapeutic requirements for various diseases serve as a guide for researchers to study natural compounds. These studies are intended to isolate, identify the structural characterization and eventually discover the pharmacological activity of natural compounds from their plant sources with the goal of treating specific diseases. Bioactive Phytochemicals: Drug Discovery to Product Development explores the scope and approaches of drug discovery from natural products. Chapters in the book cover information about the cultivation, collection and processing of medicinal plants, the methods and high throughput techniques for isolation and characterization of bioactive phytochemicals and pharmacological screening for activity, formulation and quality control. Information about the regulations specified for natural medicinal products in different region of the world is also presented, followed by a concluding chapter devoted to the role of natural herbal products for treatment of human diseases such as cancer, cardiovascular diseases, diabetes, obesity, inflammation and neurological disorders. Each chapter concludes with a general reference section, which is a bibliographic guide to more advanced texts. The contributing authors for this volume are drawn from a rich blend of experts in various areas of herbal medicine which encompass herbal drug discovery to product development. The concise and organized layout along with a broad coverage of phytochemistry and drug discovery makes this book a suitable reference for students of medicinal chemistry, researchers and industry professionals interested in herbal product development.

Both Asia and Africa are home to many plants that can be used for the treatment of many diseases and their medicinal properties are gaining interest in western societies. Medicinal plants from Asia and Africa are used for their healing abilities and also have a symbolic meaning in communities. The importance of traditional autochthonous plant remedies plays a crucial role in the health of millions of people of these two continents. Even today, traditional medicine represents the dominant medical system for millions of people showing a significant impact on health care practices. Therefore, traditional operators still represent a vital part of regional healthcare systems. For this reason, pharmaceutical industries consider traditional medicine as a source for the identification of bioactive compounds that can be used in the preparation of synthetic drugs. Biologically Active Natural Products from Asia and Africa: A Selection of Topics guides the reader to information about new natural products from these regions and the different ways to use them to treat or alleviate many of the most common diseases. The volume presents nine topics covering a number of facets of natural product medicine including: - pharmaceutical analysis of anti-diabetic herbal medicines from Bangladesh and local retailers - caffeine intake and the risk of female infertility - pharmaceutical analysis of Urena sinuata (bur mallow) - anti-CHIKV activities of diterpenes and their derivatives - anti-inflammatory nanogel for the treatment of psoriasis - antlithiatic properties of Moroccan medicinal plants - ethnobotanic, phytochemical and biological activities of Aristolochia longa L. (pipevine) - wound healing potential of combined extracts of stem bark and leaves of sphenocentrum jollyanum (an African shrub) This is a handy reference for specialists and R&D experts in pharmaceutical chemistry who wish to be informed about current knowledge on developing natural remedies in Asia and Africa

Postbiotics: Science, Technology, and Applications explains fundamental and applied knowledge about postbiotics. Chapters cover the definition and classification of postbiotics, principal methods for preparing them, information about the main postbiotic constituents and their biological activities and their clinical health benefits. The authors also familiarize the reader with potential applications of postbiotics in the food industry, pharmaceutical chemistry, medicine, and veterinary practice. The text is supported by informative illustrations, tables, and references for further reading. This comprehensive reference, with its emphasis on both basic and applied knowledge, is useful for researchers, academics, veterinarians, and students in the field of microbiology, immunology, pharmacology, biotechnology, food science, and agriculture.

Burns can cause life-threatening injury and the lengthy hospitalization and rehabilitations required in burn therapy lead to higher healthcare costs. The risk of infection has also been one of the important concerns of burn wound management. The purpose of the burn wound care management is speedy wound healing and epithelization to limit the infection. The topical application of therapeutic agents is quintessential for the longevity of patients having significant burns. In recent times, research on herbal medicine for burn wound management has been vastly increased because of their safer toxicological profiles in contrast to synthetic medicines. Despite the promising therapeutic potential of herbal medicines in this area, herbal medications have some limitations which include low pharmacological activity, solubility and stability. Nanotechnology-based smart drug delivery approaches which involve the use of small molecules as nanocarriers, however, can help to overcome these biopharmaceutical challenges. This book provides an overview of plant-mediated metallic nanoparticulate systems and nanophytomedicine based therapeutic treatment modalities for burn wound lesions. Nine chapters deliver updated information about nanomedicines for burn wound therapy. Contributions are written by experts in nanomedicine and phytomedicine and collectively cover the pathophysiology of wound lesions, current and future outlook of nanomedicine based treatments for burn wound lesions, the role of biocompatible nanomaterials in burn wound management, plant-mediated synthesis of metal nanoparticles for treating burn wound sepsis, phytomedicine based nanoformulations and the phyto-informatics models involved in the wound healing process which are used to select appropriate nanotherapeutic agents. This reference serves as an accessible source of information on the topic of nanomedicine for burn treatments for all healthcare professionals (medical doctors, nurses, students trainees) and researchers in allied fields (pharmacology, phytomedicine) who are interested in this area of medicine.