Journal
DRUG METABOLISM REVIEWS
Volume 53, Issue 2, Pages 207-233Publisher
TAYLOR & FRANCIS LTD
DOI: 10.1080/03602532.2021.1922435
Keywords
Clearance prediction; zebrafish; in-vitro in-vivo extrapolation; intrinsic clearance; in-vivo models
Categories
Funding
- National Institutes of Health [R00-ES029552]
- Swedish Research Council [2016-01153, 2016-01154, 2019-01837]
- Strategic Research Programmes in Diabetes (SFO Diabetes)
- Stem Cells and Regenerative Medicine (StratRegen)
- EU/EFPIA/OICR/McGill/KTH/Diamond Innovative Medicines Initiative 2 Joint Undertaking (EUbOPEN) [875510]
- Merck KGaA
- Eli Lilly and Company
- American Foundation for Pharmaceutical Education Predoctoral Fellowship
- NIGMS [R25 GM56847]
- Louis Zeh Fellowship
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Improved pharmacokinetics/pharmacodynamics (PK/PD) prediction in the early stages of drug development is crucial for informing lead optimization strategies and reducing attrition rates. Recent advancements in the development of new in vitro and in vivo strategies have enabled better characterization of pharmacokinetic properties and efficacy of drug leads.
Improved pharmacokinetics/pharmacodynamics (PK/PD) prediction in the early stages of drug development is essential to inform lead optimization strategies and reduce attrition rates. Recently, there have been significant advancements in the development of new in vitro and in vivo strategies to better characterize pharmacokinetic properties and efficacy of drug leads. Herein, we review advances in experimental and mathematical models for clearance predictions, advancements in developing novel tools to capture slowly metabolized drugs, in vivo model developments to capture human etiology for supporting drug development, limitations and gaps in these efforts, and a perspective on the future in the field.
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