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

Author: Yurong LAI ¹ ; Xiaoyan CHU ² ; Li DI ³ ; Wei GAO ² ; Yingying GUO ⁴ ; Xingrong LIU ⁵ ; Chuang LU ⁶ ; Jialin MAO ⁷ ; Hong SHEN ⁸ ; Huaping TANG ⁹ ; Cindy Q XIA ¹⁰ ; Lei ZHANG ¹¹ ; Xinxin DING ¹²
Author Information

1. Drug Metabolism, Gilead Sciences Inc., Foster City, CA 94404, USA.
2. Department of Pharmacokinetics, Pharmacodynamics and Drug Metabolism, Merck & Co., Inc., Kenilworth, NJ 07033, USA.
3. Pharmacokinetics, Dynamics and Metabolism, Pfizer Worldwide Research and Development, Groton, CT 06340, USA.
4. Eli Lilly and Company, Indianapolis, IN 46221, USA.
5. Drug Metabolism and Pharmacokinetics, Biogen, Cambridge, MA 02142, USA.
6. Drug Metabolism and Pharmacokinetics, Accent Therapeutics, Inc. Lexington, MA 02421, USA.
7. Department of Drug Metabolism and Pharmacokinetics, Genentech, A Member of the Roche Group, South San Francisco, CA 94080, USA.
8. Drug Metabolism and Pharmacokinetics Department, Bristol-Myers Squibb Company, Princeton, NJ 08540, USA.
9. Bioanalysis and Biomarkers, Glaxo Smith Kline, King of the Prussia, PA 19406, USA.
10. Department of Drug Metabolism and Pharmacokinetics, Takeda Pharmaceuticals International Co., Cambridge, MA 02139, USA.
11. Office of Research and Standards, Office of Generic Drugs, CDER, FDA, Silver Spring, MD 20993, USA.
12. Department of Pharmacology and Toxicology, College of Pharmacy, University of Arizona, Tucson, AZ 85721, USA.
Publication Type:Review
Keywords: ADME; Biologics license application; Drug discovery and development; Micro-physiological systems; Model-informed drug development; New drug application; New modalities; Pharmacokinetics
From: Acta Pharmaceutica Sinica B 2022;12(6):2751-2777
CountryChina
Language:English
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.