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Practical, state-of-the-art pharmacokinetic research methods, ideas, advancements, applications, and strategies

Drawing on a wealth of extensive practical experience and theoretical research, Drug Metabolism and Pharmacokinetics encapsulates the most recent advancements and illustrative applications in the field. Sixty-eight relatively independent yet interconnected articles are included, each offering a unique perspective and providing in-depth interpretation. Readers can either read systematically or select specific topics of interest from the table of contents.

Basic concepts, frontier advancements, DMPK research strategies, and technical methods are covered for novel drug modalities and therapeutics in different disease areas. The book encompasses a wide range of application and validation cases for DMPK research, including studies in in vitro ADME, in vivo pharmacokinetics, metabolite profiling and identification, radiolabeled ADME, and bioanalysis. Case studies showing the application of topics covered are included throughout, along with valuable insights into problem-solving and critical thinking.

Written by a team of scientists specializing in DMPK research from the DMPK Department of WuXi AppTec, Drug Metabolism and Pharmacokinetics discusses sample topics including:

ADME properties, metabolite identification, and bioanalytical strategies for oligonucleotide drugs Strategies and challenges in the determination of drug-to-antibody ratio (DAR) values of antibody-drug conjugates (ADCs) Breaking barriers in CNS drug development with intrathecal and intracerebroventricular administration Application and detection techniques of biomarkers in drug development Flux dialysis method for assessing plasma protein binding of high protein-binding drugs

Drug Metabolism and Pharmacokinetics is an essential forward-thinking reference on the subject for pharmacy students, pharmaceutical industry researchers, and DMPK scientists, especially those exploring novel drug modalities.

Tabla de contenidos provista por Syndetics

• About the Editors(ix)
• Preface(xi)
• Acknowledgments(xiii)
• Section I Novel Drug Modalities: Advancements and Their Pharmacokinetic Strategies(1)
• 1 Proteolysis-Targeting Chimeras (PROTACs)(3)
• 1.1 An Overview of PROTAC Technology and Drug Metabolism and Pharmacokinetic (DMPK) Research Strategies(3)
• 1.2 Strategies to Improve the Oral Bioavailability of PROTACs(9)
• 1.3 Research on PROTAC Metabolism: Strategies and Main Approaches(17)
• 1.4 Metabolic Characteristics and Research Strategies for Metabolite Identification of PROTACs(23)
• 1.5 Evaluation of Drug-Drug Interactions of PROTACs with Efflux Transporters(40)
• 1.6 PROTAC Bioanalysis: Challenges and Strategies(44)
• 2 Antibody-Drug Conjugates (ADCs)(49)
• 2.1 General Considerations for Pharmacokinetic Studies of ADCs(49)
• 2.2 Application of Integrated Bioanalysis in ADC DMPK Studies(53)
• 2.3 Study Models and Bioanalysis Methods for the Payload-Related Metabolite Identification Studies of ADCs(62)
• 2.4 Strategies and Challenges in the Determination of Drug-to-Antibody Ratio (DAR) Values for ADCs(67)
• 2.5 In Vitro Stability of ADCs in Blood Matrices(78)
• 2.6 Application of Radiolabeling Techniques in ADC Pharmacokinetic Studies(86)
• 3 Peptide-Drug Conjugates (PDCs)(95)
• 3.1 Introduction to PDCs and DMPK Research Strategies(95)
• 3.2 Targeted Release Principle and Metabolite Identification Studies of PDCs(102)
• 4 Peptide Drugs(115)
• 4.1 Development, Characteristics, and Pharmacokinetic Research Strategies of Peptide Drugs(115)
• 4.2 Metabolic Characteristics and Optimization Strategies of Peptide Drugs(123)
• 4.3 Approved Therapeutic Peptides: Strategies and Radiolabeling Considerations(132)
• 4.4 Challenges and Strategies in the Bioanalysis of Peptide Drugs(138)
• 5 Oligonucleotide (OLIGO) Drugs(147)
• 5.1 Oligonucleotide Drugs: An Introduction and Overview of Pharmacokinetic Strategies(147)
• 5.2 Delivery Systems of siRNA Drugs and Their Effects on the Pharmacokinetic Profile(152)
• 5.3 Bioanalytical Strategies for Oligonucleotide Drugs(157)
• 5.4 Oligonucleotide Drugs: Strategies for Metabolism and Metabolite Profiling and Identification(183)
• 5.5 ADME Characteristics of Approved siRNA and ASO Drugs(193)
• 6 mRNA-Based Vaccines and Therapeutics(213)
• 6.1 What Are mRNA Vaccines and Their Future(213)
• 6.2 Strategies for Preclinical PK Evaluation of mRNA-Based Therapeutics: mRNA Vaccines, mRNA Therapeutic Drugs, and Novel Excipients(221)
• 6.3 FDA-Approved mRNA Vaccines: Interpretation of Preclinical Pharmacokinetic (PK) Data(230)
• 6.4 Application of Integrative Bioanalysis in mRNA Drugs DMPK Research(235)
• Section II Pharmacokinetic and Metabolism Studies of Therapeutics for Disease Areas(243)
• 7 Ophthalmic Drugs(245)
• 7.1 Ophthalmic Drugs: Preclinical Pharmacokinetic (PK) Profiles and Research Strategies(245)
• 7.2 In Vitro Methods and Significance of Drug-Melanin Binding(253)
• 7.3 Preclinical Pharmacokinetic Research of Ophthalmic Drugs: In Vitro and In Vivo Research Methods(259)
• 7.4 In Vivo Bioanalysis in Ophthalmology: Challenges and Strategies(269)
• 8 Respiratory Drugs(275)
• 8.1 Inhaled Medications: Challenges and Strategies for Preclinical In Vivo Pharmacokinetic Studies(275)
• 8.2 Chronic Obstructive Pulmonary Disease (COPD): Analysis of PK Profiles of Approved Inhaled Medications(285)
• 9 Transdermal and Topical Drugs(291)
• 9.1 Preclinical Pharmacokinetic Strategies for Topical and Transdermal Drug Products(291)
• 9.2 Application of In Vitro Permeation Test (IVPT) for the Development of Transdermal and Topical Drugs(300)
• 9.3 Evaluation of Transdermal Drugs in In Vivo Pharmacokinetic Studies(308)
• 9.4 Challenges and Bioanalytical Strategies for Quantitative Detection of In Vivo Biological Samples from Skin Administration(313)
• 10 Central Nervous System Drugs(317)
• 10.1 Overview of Pharmacokinetic Research Strategies for Central Nervous System Drugs(317)
• 10.2 Application of Microdialysis in Pharmacokinetic Research(329)
• 10.3 Central Nervous System Drug Development Techniques: Exploration and Application in Large Animal Pharmacokinetics(337)
• Section III Research Strategies, Methods, and Applications in Pharmacokinetics and Metabolism(343)
• 11 In Vitro ADME(345)
• 11.1 Rapid Determination of Lipophilicity: Establishment and Application of Reversed-Phase High-Performance Liquid Chromatography (RP-HPLC)(345)
• 11.2 Plasma Protein Binding Measurement of High Protein-Binding Drugs: Principles and Advantages of the Flux Dialysis Method(351)
• 11.3 How to Measure the Metabolic Clearance of Slowly Metabolized Compounds(358)
• 11.4 Enzyme-Mediated Metabolism and In Vitro Assessment Method(365)
• 11.5 Time-Dependent Inhibition (TDI): A Novel Area Under the Curve Shift (AUC Shift) Approach(377)
• 11.6 Reaction Phenotyping for Four Additional CYPs: Why and How(383)
• 11.7 Overview of the Application of the Na+-Taurocholate Cotransporting Polypeptide (NTCP) in Drug Development(388)
• 11.8 The Significance and In Vitro Methods of Lysosomal Trapping in Drug Development(397)
• 12 In Vivo Pharmacokinetics(407)
• 12.1 Enhancing the Bioavailability of Poorly Soluble Compounds: Strategies for Formulation Optimization in Preclinical Studies(407)
• 12.2 Self-Emulsifying Drug Delivery System (SEDDS): Enhancing the Oral Absorption of Lipophilic Compounds(414)
• 12.3 Application of Anesthetics in Rodent Pharmacokinetic Studies(420)
• 12.4 Application of In Situ Single-Pass Intestinal Perfusion (SPIP) Model in the Study of Intestinal Absorption of Oral Drugs(428)
• 12.5 Application of Liver Biopsy in Preclinical Pharmacokinetic Studies(436)
• 13 Metabolite Profiling and Identification(441)
• 13.1 High-Throughput Identification of Drug Metabolic Soft Spots for Lead Optimization(441)
• 13.2 Application of Metabolite Biosynthesis Technology in the Precise Identification of Drug Metabolite Structures(449)
• 13.3 Detection of Reactive Metabolites and Its Application in Drug Research and Development(456)
• 13.4 UGT Enzymes: Metabolite Identification and Toxicity Assessment Strategies(466)
• 13.5 Insights into the R&D Strategies of Deuterated Drugs from the Drug Metabolism Perspective(472)
• 14 Radiolabeled In Vivo ADME Studies(479)
• 14.1 Placental Transfer and Milk Excretion Studies Based on Radioactive Tracer Technique(479)
• 14.2 Visualization of Tissue Distribution: Quantitative Whole-Body Autoradiography (QWBA)(486)
• 14.3 Preclinical and Clinical Research Strategy for Human Radiolabeled Mass Balance Studies(490)
• 14.4 Key Considerations for Conducting Radiolabeled Human Mass Balance Studies(496)
• 15 Bioanalysis(503)
• 15.1 Application of High-Throughput Mass Spectrometry in In Vitro ADME(503)
• 15.2 Application and Detection Techniques of Biomarkers in Drug Development(510)
• 15.3 Analysis and Detection Strategies of Liposome Drugs in Biological Samples(516)
• 15.4 DMPK Research Strategies of Chiral Drugs Based on UPCC-MS/MS and UPLC-MS/MS Dual Analytical Platforms(523)
• 15.5 Integrated Qualitative and Quantitative Bioanalysis of Intact Protein with High-Resolution Mass Spectrometry(530)
• 15.6 Nanobodies: Kinetics and Bioanalytical Strategies(540)
• Index(549)

Notas de autor provistas por Syndetics

Liang Shen, PhD, is the head of DMPK at WuXi AppTec.