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Recent advances in the translation of drug metabolism and pharmacokinetics science for drug discovery and development

Yurong Lai,  Xiaoyan Chu,  Li Di,  Wei Gao,  Yingying Guo,  Xingrong Liu,  Chuang Lu,  Jialin Mao,  Hong Shen,  Huaping Tang,  Cindy Q. Xia,  Lei Zhang,  Xinxin Ding

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Yurong Lai, Xiaoyan Chu, Li Di, Wei Gao, Yingying Guo, Xingrong Liu, Chuang Lu, Jialin Mao, Hong Shen, Huaping Tang, Cindy Q. Xia, Lei Zhang, Xinxin Ding. Recent advances in the translation of drug metabolism and pharmacokinetics science for drug discovery and development[J]. 机械工程学报. doi: 10.1016/j.apsb.2022.03.009
引用本文: Yurong Lai, Xiaoyan Chu, Li Di, Wei Gao, Yingying Guo, Xingrong Liu, Chuang Lu, Jialin Mao, Hong Shen, Huaping Tang, Cindy Q. Xia, Lei Zhang, Xinxin Ding. Recent advances in the translation of drug metabolism and pharmacokinetics science for drug discovery and development[J]. 机械工程学报. doi: 10.1016/j.apsb.2022.03.009
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Yurong Lai, Xiaoyan Chu, Li Di, Wei Gao, Yingying Guo, Xingrong Liu, Chuang Lu, Jialin Mao, Hong Shen, Huaping Tang, Cindy Q. Xia, Lei Zhang, Xinxin Ding. Recent advances in the translation of drug metabolism and pharmacokinetics science for drug discovery and development[J]. JOURNAL OF MECHANICAL ENGINEERING. doi: 10.1016/j.apsb.2022.03.009
Citation: Yurong Lai, Xiaoyan Chu, Li Di, Wei Gao, Yingying Guo, Xingrong Liu, Chuang Lu, Jialin Mao, Hong Shen, Huaping Tang, Cindy Q. Xia, Lei Zhang, Xinxin Ding. Recent advances in the translation of drug metabolism and pharmacokinetics science for drug discovery and development[J]. JOURNAL OF MECHANICAL ENGINEERING. doi: 10.1016/j.apsb.2022.03.009
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Recent advances in the translation of drug metabolism and pharmacokinetics science for drug discovery and development

doi: 10.1016/j.apsb.2022.03.009

  • a. Drug Metabolism, Gilead Sciences Inc., Foster City, CA 94404, USA;

  • b. Department of Pharmacokinetics, Pharmacodynamics and Drug Metabolism, Merck & Co., Inc., Kenilworth, NJ 07033, USA;

  • c. Pharmacokinetics, Dynamics and Metabolism, Pfizer Worldwide Research and Development, Groton, CT 06340, USA;

  • d. Eli Lilly and Company, Indianapolis, IN 46221, USA;

  • e. Drug Metabolism and Pharmacokinetics, Biogen, Cambridge, MA 02142, USA;

  • f. Drug Metabolism and Pharmacokinetics, Accent Therapeutics, Inc. Lexington, MA 02421, USA;

  • g. Department of Drug Metabolism and Pharmacokinetics, Genentech, A Member of the Roche Group, South San Francisco, CA 94080, USA;

  • h. Drug Metabolism and Pharmacokinetics Department, Bristol-Myers Squibb Company, Princeton, NJ 08540, USA;

  • i. Bioanalysis and Biomarkers, Glaxo Smith Kline, King of the Prussia, PA 19406, USA;

  • j. Department of Drug Metabolism and Pharmacokinetics, Takeda Pharmaceuticals International Co., Cambridge, MA 02139, USA;

  • k. Office of Research and Standards, Office of Generic Drugs, CDER, FDA, Silver Spring, MD 20993, USA;

  • l. Department of Pharmacology and Toxicology, College of Pharmacy, University of Arizona, Tucson, AZ 85721, USA

基金项目: 

We would like to thank Dr. Ping Zhao and Dr. Donglu Zhang for providing scientific insights on this review article. Research in Xinxin Ding's laboratory was supported in part by grants from the National Institutes of Health (CA023074, CA092596, ES004940, ES006694, and ES020867, USA).

详细信息
    通讯作者:

    Yurong Lai,E-mail:Yurong.lai@gilead.com

    Xinxin Ding,E-mail:xding@pharmacy.arizona.edu

  • 中图分类号: https://www.sciencedirect.com/science/article/pii/S2211383522001083/pdf?md5=c46dcd9d5479b580a38bd281101c0b7f&pid=1-s2.0-S2211383522001083-main.pdf

Recent advances in the translation of drug metabolism and pharmacokinetics science for drug discovery and development

  • a. Drug Metabolism, Gilead Sciences Inc., Foster City, CA 94404, USA;

  • b. Department of Pharmacokinetics, Pharmacodynamics and Drug Metabolism, Merck & Co., Inc., Kenilworth, NJ 07033, USA;

  • c. Pharmacokinetics, Dynamics and Metabolism, Pfizer Worldwide Research and Development, Groton, CT 06340, USA;

  • d. Eli Lilly and Company, Indianapolis, IN 46221, USA;

  • e. Drug Metabolism and Pharmacokinetics, Biogen, Cambridge, MA 02142, USA;

  • f. Drug Metabolism and Pharmacokinetics, Accent Therapeutics, Inc. Lexington, MA 02421, USA;

  • g. Department of Drug Metabolism and Pharmacokinetics, Genentech, A Member of the Roche Group, South San Francisco, CA 94080, USA;

  • h. Drug Metabolism and Pharmacokinetics Department, Bristol-Myers Squibb Company, Princeton, NJ 08540, USA;

  • i. Bioanalysis and Biomarkers, Glaxo Smith Kline, King of the Prussia, PA 19406, USA;

  • j. Department of Drug Metabolism and Pharmacokinetics, Takeda Pharmaceuticals International Co., Cambridge, MA 02139, USA;

  • k. Office of Research and Standards, Office of Generic Drugs, CDER, FDA, Silver Spring, MD 20993, USA;

  • l. Department of Pharmacology and Toxicology, College of Pharmacy, University of Arizona, Tucson, AZ 85721, USA

Funds: 

We would like to thank Dr. Ping Zhao and Dr. Donglu Zhang for providing scientific insights on this review article. Research in Xinxin Ding's laboratory was supported in part by grants from the National Institutes of Health (CA023074, CA092596, ES004940, ES006694, and ES020867, USA).

    摘要
  • 摘要: Drug metabolism and pharmacokinetics (DMPK) is an important branch of pharmaceutical sciences. The nature of ADME (absorption, distribution, metabolism, excretion) and PK (pharmacokinetics) inquiries during drug discovery and development has evolved in recent years from being largely descriptive to seeking a more quantitative and mechanistic understanding of the fate of drug candidates in biological systems. Tremendous progress has been made in the past decade, not only in the characterization of physiochemical properties of drugs that influence their ADME, target organ exposure, and toxicity, but also in the identification of design principles that can minimize drug-drug interaction (DDI) potentials and reduce the attritions. The importance of membrane transporters in drug disposition, efficacy, and safety, as well as the interplay with metabolic processes, has been increasingly recognized. Dramatic increases in investments on new modalities beyond traditional small and large molecule drugs, such as peptides, oligonucleotides, and antibody-drug conjugates, necessitated further innovations in bioanalytical and experimental tools for the characterization of their ADME properties. In this review, we highlight some of the most notable advances in the last decade, and provide future perspectives on potential major breakthroughs and innovations in the translation of DMPK science in various stages of drug discovery and development.

     

    Abstract: Drug metabolism and pharmacokinetics (DMPK) is an important branch of pharmaceutical sciences. The nature of ADME (absorption, distribution, metabolism, excretion) and PK (pharmacokinetics) inquiries during drug discovery and development has evolved in recent years from being largely descriptive to seeking a more quantitative and mechanistic understanding of the fate of drug candidates in biological systems. Tremendous progress has been made in the past decade, not only in the characterization of physiochemical properties of drugs that influence their ADME, target organ exposure, and toxicity, but also in the identification of design principles that can minimize drug-drug interaction (DDI) potentials and reduce the attritions. The importance of membrane transporters in drug disposition, efficacy, and safety, as well as the interplay with metabolic processes, has been increasingly recognized. Dramatic increases in investments on new modalities beyond traditional small and large molecule drugs, such as peptides, oligonucleotides, and antibody-drug conjugates, necessitated further innovations in bioanalytical and experimental tools for the characterization of their ADME properties. In this review, we highlight some of the most notable advances in the last decade, and provide future perspectives on potential major breakthroughs and innovations in the translation of DMPK science in various stages of drug discovery and development.

     

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  • 收稿日期:  2021-09-22
  • 修回日期:  2021-11-07
  • 录用日期:  2021-11-10
  • 网络出版日期:  2023-03-17

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