Drug Metabolism and Pharmacokinetics: Frontiers, Strategies, and Applications

Publications
Jun 13, 2025

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.

◢ Edited by Liang Shen and WuXi AppTec DMPK
◢ ISBN: 978-1-394-30012-9, July 2025, 576 pages

Access a Free Chapter on PROTACS

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.

Access a Free Chapter on PROTACS

*Click here to download PDF version.

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 Insights into ADME Studies of 37 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: Principlesand Advantages of the Flux Dialysis Method 351

11.3 How to Measure the Metabolic Clearance of Slowly Metabolized Compounds 358

11.4 Non-P450 Enzyme-Mediated Metabolism and In Vitro Assessment Method 365

11.5 In Vitro Evaluation of CYP450 Time-Dependent Inhibition (TDI): A Novel Area Under the Curve Shift (AUC Shift) Approach 377

11.6 Cytochrome P450 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

Scroll down for more

About the Author

Liang Shen

Ph.D., Vice President, Head of DMPK Department, WuXi AppTec

Dr. Liang Shen has more than 20 years of experience in drug metabolism and pharmacokinetics (DMPK), toxicology, clinical pharmacology, and precision medicine. Dr. Shen has published or co-authored over 50 research articles and has led or participated in the compilation or translation of four books in drug discovery or DMPK field. His extensive experience in drug discovery, preclinical candidate (PCC) profiling, and investigational new drug (IND) submissions has successfully supported multiple pipelines in the fields of oncology, immuno-oncology, immunology, metabolic diseases, infectious diseases, central nervous system (CNS), and cardiovascular diseases to proof-of-concept at the early clinical stage. He received his PhD degree from the University of Georgia in the United States.

WuXi AppTec DMPK

As a global company with operations across Asia, Europe, and North America, WuXi AppTec provides a broad portfolio of R&D and manufacturing services that enable the global pharmaceutical and life sciences industry to advance discoveries and deliver groundbreaking treatments to patients. The Department of DMPK of WuXi AppTec was established in 2006 and offers in vivo and in vitro DMPK services covering stages from discovery screening to preclinical development and clinical studies. With research facilities located in the United States (New Jersey) and China (Shanghai, Suzhou, Nanjing, and Nantong), the department has supported thousands of investigational new drug (IND) and new drug applications (NDA).The services of WuXi AppTec DMPK include in vitro absorption, distribution, metabolism, excretion (ADME) studies, in vivo pharmacokinetic studies, metabolite profiling and identification studies, synthesis of radiolabeled compounds, radiolabeled ADME including human absorption, metabolism, and excretion (AME) studies, and bioanalysis. For more information, visit dmpkservice.wuxiapptec.com.

Acknowledgments

The compilation and publication of this book have been a joint effort. Credit should be given to the authors and editors, who have delivered profound insights by drawing upon their vast DMPK expertise. Their hard work, research, and commitment in crafting this book deserve special recognition. We would like to thank all the authors and editors, listed here in alphabetical order.

Peiyun An, Weiqun Cao, Dr. Genfu Chen, Dr. Jacob Zhi Chen, Dr. Shiyan Chen, Song Chen, Yu Chen, Liwei Cheng, Dr. Qigan Cheng, Hongfang Cui, Qian Cui, Tiantian Dang, Ya Ding, Xuan Dong, Jian Fang, Quanli Feng, Flora Fu, Xinfa Fu, Li Gao, Lijia Gao, Yafei Gao, Yang Gao, Lian Guo, Qiqi Han, Huan He, Lijuan Hou, Jie Hu, Weimin Hu, Dr. Jiaming Jiang, Dr. Lifang Jiang, Dr. Furong Jiao, Dr. Jing Jin, Wei Lei, Chengyuan Li, Hongye Li, Huan Li, Huayu Li, Dr. Huihui Li, Jie Li, Lin Li, Dr. Peng Li, Qian Li, Ruixing Li, Tingting Li, Xiaotong Li, Xin Li, Yingying Li, Zhihai Li, Dr. Zhiyu Li, Danqing Lin, Haijuan Liu, Dr. Huan Liu, Huan Liu, Jian Liu, Mengjie Liu, Qing Liu, Shoutao Liu, Siyu Liu, Yanfeng Liu, Chunhong Lu, Jinlian Lu, Yikuan Lu, Dr. Dongke Ma, Dr. Liping Ma, Chen Ning, Jie Pan, Dr. Yan Pan, Linlin Pei, Hongfeng Qian, Huijuan Qian, Gengyao Qin, Dr. Li Qu, Xiang Ren, Yanfu Ren, Tingting Ruan, Dr. Liang Shen, Dr. Liqi Shi, Xinmeng Shi, Miaomiao Song, Yuanqiang Su, Hong Sun, Jianping Sun, Ziqian Sun, Cheng Tang, Liping Tang, Xue Tang, Dr. Yi Tao, Binbin Tian, Dr. Hongmei Wang, Huijuan Wang, Dr. Jie Wang, Junjie Wang, Dr. Xiangling Wang, Dr. Xiaoqi Wang, Yu Wang, Yuxi Wang, Xinxin Wen, Lili Xing, Haiwei Xiong, Tao Xiong, Dr. Mingcheng Xu, Ye Xu, Jia Xue, Dr. Huan Yan, Jinyu Yan, Dr. Yunyi Yan, Guang Yang, Rong Yang, Xianqing Yu, Dr. Jiaqi Yuan, Chao Zhang, Hefeng Zhang, Dr. Hong Zhang, Honghong Zhang, Dr. Lingling Zhang, Xuan Zhang, Yingying Zhang, Yu Zhang, Hang Zhao, Dr. Nan Zhao, Lijin Zheng, Dr. Maotian Zhou, Xinyun Zhou, Ying Zhou, Wenjun Zhu, and Zhangpei Zhu.

Receive DMPK email updates

Talk to an Expert

Related Services and Platforms

Stay Connected

Keep up with the latest news and insights.

Email address*

* Please check the filled content
First name*

* Please check the filled content
Last name*

* Please check the filled content
Company*

* Please check the filled content

By clicking submit, you consent to WuXi AppTec DMPK collecting and processing the information you provide for our internal purposes, in accordance with our privacy policy.

* Please agree to the Privacy Policy

Submit