Download or read book An Investigation of the Impact of Intestinal Lymphatic Transport on Bioavailability Systemic Clearance and Disposition of Lipophilic Drugs written by Suzanne Mary Caliph and published by . This book was released on 2013 with total page 524 pages. Available in PDF, EPUB and Kindle. Book excerpt: Highly lipophilic and poorly water soluble drug candidates are common outcomes ofdrug discovery programs in recent years, presenting drug development challenges throughpoor gastrointestinal absorption and insufficient systemic exposure after oral administration.Co-administration with lipidic excipients presents an apparent strategy to improve the oralbioavailability of these compounds by stimulating enhanced solubilisation in the gut andrecruitment of intestinal lymphatic drug transport. The impact of stimulating intestinallymphatic transport to improve oral bioavailability on systemic drug exposure, clearance anddeposition has been poorly understood. The interpretation of lymphatic drug transport data isfurther complicated by variations in dosing excipients and dispersed states, study models,prandial (fed/fasted) states, intravenous dosing conditions and formulations used for theassessment of absolute bioavailability. The studies described in this thesis investigatedvarious factors affecting the intestinal lymphatic transport and oral bioavailability assessmentof highly lipophilic compounds using lymph-cannulated and non lymph-cannulated animals.These factors examined included subtle differences in lipophilicity and lipid solubility ofchemically similar drug analogues, lipid and non-lipid based oral formulations, intravenousdosing states and dosing conditions. The impact of lymphatic drug delivery on systemicexposure, clearance and drug deposition was also examined in comparison with portal routeof drug absorption in this thesis. Oral bioavailability of highly lipophilic analogues wassignificantly enhanced after administration in long chain lipid-based formulations viastimulation of intestinal lymphatic transport and significantly influenced by subtle differencesin lipid solubility, however, not lipophilicity as indicated by log P. After delivery in lymph orthe lipid-based emulsion, systemic clearance (Cl) and volume of distribution (Vd) of a highlylipophilic, lymphatically transported model drug, halofantrine (Hf) were significantly lowerthan when delivered in plasma or lipid-free co-solvent formulation. However, where drug andlipid entered the systemic circulation coincidentally, Cl and Vd were unaffected by the routeof entry, but significantly altered by total plasma lipid levels. These findings suggest that amismatch in plasma lipid levels after intravenous and oral administration may lead todifferences in drug clearance and errors in bioavailability assessment. This thesis alsoinvestigated the influence of absorption route (lymphatics vs. blood) on drugpharmacokinetics and tissue distribution. Brain to blood ratios were found to be significantlylower after stimulation of intestinal lymphatic delivery suggesting that drug association withintestinal lymph lipoproteins might limit brain drug access. Lipophilic model compounds(DDT, Hf) and lipids were assessed following delivery to the systemic circulation inassociation with lymph lipoproteins or plasma, and were found to differ significantly. ForDDT, Cl and Vd were higher whereas for Hf, these parameters were lower due, in particular,to differences in adipose tissue uptake and liver uptake. For compounds like DDT, changes tothe route of absorption may thus directly impact on pharmacokinetics and tissue distribution,whereas for Hf, factors which influence lymphatic transport may, by altering systemiclipoprotein concentrations, indirectly impact pharmacokinetics and tissue distribution.Ultimately, careful control of dosing conditions and thus the extent of lymphatic transportmay be important in assuring reproducible efficacy and toxicity for lymphatically transporteddrugs.
Download or read book Lymphatic Transport of Drugs written by William N. Charman and published by Routledge. This book was released on 2019-05-23 with total page 348 pages. Available in PDF, EPUB and Kindle. Book excerpt: Lymphatic Transport of Drugs provides a thorough review of the determinants that affect the uptake and delivery of drugs and xenobiotics to the lymphatics. Factors affecting the transport and delivery of lipophilic drugs through the lymph after oral administration, lymphatic transport of polar drugs and macromolecules after gastrointestinal dosing, transport of drugs into the lymph after parenteral administration, and particulate drug delivery systems are among the topics examined in this volume. Lymphatic Transport of Drugs is primarily intended for pharmaceutical scientists who are attempting to alter the delivery of current therapeutic agents through formulation of prodrugs, as well as for researchers designing new drugs for lymph delivery.
Download or read book Lipids to Improve Intestinal Lymphatic Drug Transport written by Bhupendra G. Prajapati and published by LAP Lambert Academic Publishing. This book was released on 2012 with total page 56 pages. Available in PDF, EPUB and Kindle. Book excerpt: After oral administration, the majority of drug molecules are absorbed across the small intestine and enter the systemic circulation via the portal vein and the liver. For some highly lipophilic drugs (typically log PN5, lipid solubility 50 mg/g), however, association with lymph lipoproteins in the enterocyte leads to transport to the systemic circulation via the intestinal lymph. The attendant delivery benefits associated with lymphatic drug transport include a reduction in first pass metabolism and lymphatic exposure to drug concentrations orders of magnitude higher than that attained in systemic blood. In the current review we briefly describe the mechanisms by which drug molecules access the lymph and the formulation strategies that may be utilised to enhance lymphatic drug transport. Specific focus is directed toward recent advances in understanding regarding the impact of lipid source (both endogenous and exogenous) and intracellular lipid trafficking pathways on lymphatic drug transport and enterocyte based first pass metabolism.
Download or read book Oral Drug Absorption written by Jennifer B. Dressman and published by CRC Press. This book was released on 2016-04-19 with total page 432 pages. Available in PDF, EPUB and Kindle. Book excerpt: Oral Drug Absorption, Second Edition thoroughly examines the special equipment and methods used to test whether drugs are released adequately when administered orally. The contributors discuss methods for accurately establishing and validating in vitro/in vivo correlations for both MR and IR formulations, as well as alternative approaches for MR an
Download or read book Drug Absorption Studies written by Carsten Ehrhardt and published by Springer Science & Business Media. This book was released on 2007-12-22 with total page 711 pages. Available in PDF, EPUB and Kindle. Book excerpt: This is a well thought-out, highly practical text covering contemporary ‘in vitro’ techniques for drug absorption studies. Starting at the molecular level of investigation, it continues with cell monolayer models (both primary and cell lines) and culminates with in situ techniques as a final testing format. In addition, chapters on high-throughput assays, in vitro-in vivo correlation, bioinformatics and regulatory issues are covered, giving a comprehensive overview of available models and techniques. Moreover, an appendix consisting of a number of practical protocols is available online, updated as needed, and should prove very helpful to apply the techniques directly to the benchside.
Download or read book Drug Transporters written by Martin F. Fromm and published by Springer Science & Business Media. This book was released on 2010-11-19 with total page 457 pages. Available in PDF, EPUB and Kindle. Book excerpt: It is increasingly recognized that various transporter proteins are expressed throughout the body and determine absorption, tissue distribution, biliary and renal elimination of endogenous compounds and drugs and drug effects. This book will give an overview on the transporter families which are most important for drug therapy. Most chapters will focus on one transporter family highlighting tissue expression, substrates, inhibitors, knock-out mouse models and clinical studies.
Download or read book Toxicological Profile for Polycyclic Aromatic Hydrocarbons written by and published by . This book was released on 1995 with total page 500 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Handbook of Drug Nutrient Interactions written by Joseph I. Boullata and published by Springer Science & Business Media. This book was released on 2010-03-17 with total page 823 pages. Available in PDF, EPUB and Kindle. Book excerpt: Handbook of Drug-Nutrient Interactions, Second Edition is an essential new work that provides a scientific look behind many drug-nutrient interactions, examines their relevance, offers recommendations, and suggests research questions to be explored. In the five years since publication of the first edition of the Handbook of Drug-Nutrient Interactions new perspectives have emerged and new data have been generated on the subject matter. Providing both the scientific basis and clinical relevance with appropriate recommendations for many interactions, the topic of drug-nutrient interactions is significant for clinicians and researchers alike. For clinicians in particular, the book offers a guide for understanding, identifying or predicting, and ultimately preventing or managing drug-nutrient interactions to optimize patient care. Divided into six sections all chapters have been revised or are new to this edition. Chapters balance the most technical information with practical discussions and include outlines that reflect the content; discussion questions that can guide the reader to the critical areas covered in each chapter, complete definitions of terms with the abbreviation fully defined and consistent use of terms between chapters. The editors have performed an outstanding service to clinical pharmacology and pharmaco-nutrition by bringing together a multi-disciplinary group of authors. Handbook of Drug-Nutrient Interactions, Second Edition is a comprehensive up-to-date text for the total management of patients on drug and/or nutrition therapy but also an insight into the recent developments in drug-nutrition interactions which will act as a reliable reference for clinicians and students for many years to come.
Download or read book Handbook of Basic Pharmacokinetics Including Clinical Applications written by Wolfgang A. Ritschel and published by . This book was released on 1992 with total page 616 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Oral Delivery of Therapeutic Peptides and Proteins written by Puneet Tyagi and published by Elsevier. This book was released on 2022-08-15 with total page 316 pages. Available in PDF, EPUB and Kindle. Book excerpt: Oral Delivery of Therapeutic Peptides and Proteins provides a complete overview of the journey scientists pursue to attain protein and peptide oral delivery. The book highlights the physiological challenges that must be accounted for in addition to overcoming protease inhibition and acid stability issues that are commonly mentioned in this area of research. Primary topics include formulation technologies being adopted for oral delivery of proteins and peptides, modification of actives to make them more suited for oral delivery, animal models and their shortcomings in assessing oral bioavailability, and in vitro models to simulate drug absorption and transport. Academics and industry researchers working in formulation development and researchers and advanced students in biotechnology and pharmacy will find this a useful resource. Demonstrates how proteins and peptides transport throughout the gastrointestinal tract and how to evaluate their biological fate when encapsulated into certain delivery systems Examines developing technologies to improve future oral bioavailability Includes the in vitro and preclinical techniques needed for development
Download or read book Nanopharmaceuticals Principles and Applications Vol 3 written by Vinod Kumar Yata and published by Springer Nature. This book was released on 2020-08-19 with total page 340 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book is the third volume on this subject and focuses on the recent advances of nanopharmaceuticals in cancer, dental, dermal and drug delivery applications and presents their safety, toxicity and therapeutic efficacy. The book also includes the transport phenomenon of nanomaterials and important pathways for drug delivery applications. It goes on to explain the toxicity of nanoparticles to different physiological systems and methods used to assess this for different organ systems using examples of in vivo systems.
Download or read book Controlled Pulmonary Drug Delivery written by Hugh D.C. Smyth and published by Springer Science & Business Media. This book was released on 2011-06-24 with total page 560 pages. Available in PDF, EPUB and Kindle. Book excerpt: The pace of new research and level of innovation repeatedly introduced into the field of drug delivery to the lung is surprising given its state of maturity since the introduction of the pressurized metered dose inhaler over a half a century ago. It is clear that our understanding of pulmonary drug delivery has now evolved to the point that inhalation aerosols can be controlled both spatially and temporally to optimize their biological effects. These abilities include controlling lung deposition, by adopting formulation strategies or device technologies, and controlling drug uptake and release through sophisticated particle technologies. The large number of contributions to the scientific literature and variety of excellent texts published in recent years is evidence for the continued interest in pulmonary drug delivery research. This reference text endeavors to bring together the fundamental theory and practice of controlled drug delivery to the airways that is unavailable elsewhere. Collating and synthesizing the material in this rapidly evolving field presented a challenge and ultimately a sense of achievement that is hopefully reflected in the content of the volume.
Download or read book Toxicological Profile for Pyrethrins and Pyrethroids written by and published by . This book was released on 2003 with total page 334 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Drug Metabolism written by Mino R. Caira and published by Springer Science & Business Media. This book was released on 2006-07-10 with total page 431 pages. Available in PDF, EPUB and Kindle. Book excerpt: Drug Metabolism: Current Concepts provides a comprehensive understanding of the processes that take place following ingestion of a medicinal agent or xenobiotic, with an emphasis on the crucial role of metabolism (biotransformation). How a sound knowledge of these phenomena is incorporated into the design of effective new drug candidates is also explained. The user-friendly text focuses on concepts rather than extraneous details and is supported by many illustrated examples of biotransformations as well as frequent references to current critical reviews and articles highlighting the nature of research objectives in this vibrant area of medicinal development. The final topic on strategies for drug design relies on the background provided by the rest of the book. This book is ideally suited as an advanced text for courses in drug metabolism for students of medicine, pharmacy, pharmacology, biochemistry; and for courses in drug design and drug delivery for students of medicinal chemistry. It is also appropriate for professional seminars or courses that relate to the fate of a drug in the body, drug interactions, adverse reactions and drug design.
Download or read book Handbook of Drug Monitoring Methods written by Amitava Dasgupta and published by Springer Science & Business Media. This book was released on 2007-10-23 with total page 441 pages. Available in PDF, EPUB and Kindle. Book excerpt: Written in a handbook style with specific methods and tips on eliminating false positive and false negative results, this book is a practical guide to the detailed mechanisms of such occurrences.
Download or read book Drug Delivery written by Binghe Wang and published by John Wiley & Sons. This book was released on 2016-04-18 with total page 740 pages. Available in PDF, EPUB and Kindle. Book excerpt: Following its successful predecessor, this book covers the fundamentals, delivery routes and vehicles, and practical applications of drug delivery. In the 2nd edition, almost all chapters from the previous are retained and updated and several new chapters added to make a more complete resource and reference. • Helps readers understand progress in drug delivery research and applications • Updates and expands coverage to reflect advances in materials for delivery vehicles, drug delivery approaches, and therapeutics • Covers recent developments including transdermal and mucosal delivery, lymphatic system delivery, theranostics • Adds new chapters on nanoparticles, controlled drug release systems, theranostics, protein and peptide drugs, and biologics delivery
Download or read book Role of Lipid Excipients in Modifying Oral and Parenteral Drug Delivery written by Kishor M. Wasan and published by John Wiley & Sons. This book was released on 2007-01-09 with total page 217 pages. Available in PDF, EPUB and Kindle. Book excerpt: This comprehensive resource covers the fundamentals, formulation, and biopharmaceutical issues of lipid-based drug delivery. It presents the principles of lipid absorption and covers formulation issues, such as dissolution testing and stability testing, and physiological and biopharmaceutical issues, including the role of specific enzymes, the evaluation of transport systems in the body, and the mechanisms governing the transport of water-insoluble drugs.
