Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Comment
  • Published:

Modelling patient drug exposure profiles in vitro to narrow the valley of death

Nature Reviews Bioengineering volume 2, pages 196–197 (2024)Cite this article

Subjects

The current drug development pipeline is time-consuming, costly and inefficient. To better model interactions between pharmaceuticals and human physiology and, thus, increase the likelihood of drug success in clinical trials, the effect of pharmacokinetic drug profiles on cellular behaviour should be tested early in drug development.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: In vitro testing of in vivo pharmacokinetic (PK) profiles.

References

  1. Chi, L. H., Burrows, A. D. & Anderson, R. L. Can preclinical drug development help to predict adverse events in clinical trials? Drug Discov. Today 27, 257–268 (2022).

    Article  CAS  PubMed  Google Scholar 

  2. Sun, D., Gao, W., Hu, H. & Zhou, S. Why 90% of clinical drug development fails and how to improve it? Acta Pharm. Sin. B 12, 3049–3062 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Guerrero, Y. A. et al. A microfluidic perfusion platform for in vitro analysis of drug pharmacokinetic-pharmacodynamic (PK-PD) relationships. AAPS J. 22, 53 (2020).

    Article  CAS  PubMed  Google Scholar 

  4. Singh, D. et al. A microfluidic system that replicates pharmacokinetic (PK) profiles in vitro improves prediction of in vivo efficacy in preclinical models. PLOS Biol. 20, e3001624–e3001624 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Thiemicke, A. & Neuert, G. Rate thresholds in cell signaling have functional and phenotypic consequences in non-linear time-dependent environments. Front. Cell Dev. Biol. 11, 1124874 (2023).

    Article  PubMed  PubMed Central  Google Scholar 

  6. Lohasz, C. et al. A microphysiological cell-culturing system for pharmacokinetic drug exposure and high-resolution imaging of arrays of 3D microtissues. Front. Pharmacol. 12, 785851 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Petreus, T. et al. Tumour-on-chip microfluidic platform for assessment of drug pharmacokinetics and treatment response. Commun. Biol. 4, 1001 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Kolluri, S., Lin, J., Liu, R., Zhang, Y. & Zhang, W. Machine learning and artificial intelligence in pharmaceutical research and development: a review. AAPS J. 24, 19 (2022).

    Article  PubMed  Google Scholar 

  9. Jashnsaz, H. et al. Diverse cell stimulation kinetics identify predictive signal transduction models. iScience 23, 101565 (2020).

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  10. Thiemicke, A., Jashnsaz, H., Li, G. & Neuert, G. Generating kinetic environments to study dynamic cellular processes in single cells. Sci. Rep. 9, 10129 (2019).

    Article  ADS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

G.N. is supported by National Institutes of Health (NIH) R01GM140240 and Vanderbilt Basic Science Dean’s Faculty Fellow Endowed Chair.

Author information

Authors and Affiliations

  1. The Office of Biomedical Research Education and Training, Vanderbilt University School of Medicine, Nashville, TN, USA

    Catherine S. Leasure

  2. Department of Molecular Physiology and Biophysics, School of Medicine, Vanderbilt University, Nashville, TN, USA

    Catherine S. Leasure & Gregor Neuert

  3. Vanderbilt Institute for Infection, Immunology, and Inflammation, Vanderbilt University Medical Center, Nashville, TN, USA

    Gregor Neuert

  4. Department of Biomedical Engineering, School of Engineering, Vanderbilt University, Nashville, TN, USA

    Gregor Neuert

  5. Department of Pharmacology, School of Medicine, Vanderbilt University, Nashville, TN, USA

    Gregor Neuert

  6. Center for Applied Artificial Intelligence in Protein Dynamics, Vanderbilt University, Nashville, TN, USA

    Gregor Neuert

  7. Quantitative Systems Biology Center, Vanderbilt University, Nashville, TN, USA

    Gregor Neuert

  8. Vanderbilt Center for Stem Cell Biology, Vanderbilt University, Nashville, TN, USA

    Gregor Neuert

  9. Vanderbilt Institute of Chemical Biology, Vanderbilt University, Nashville, TN, USA

    Gregor Neuert

Authors
  1. Catherine S. Leasure
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Gregor Neuert
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

C.S.L. and G.N. conceived the concept for the article and C.S.L. drafted the manuscript. G.N. critically reviewed and edited the manuscript.

Corresponding author

Correspondence to Gregor Neuert.

Ethics declarations

Competing interests

G.N. is a co-inventor of the pending patent WO2023220749A2. C.S.L. declares no competing interests.

Additional information

Related links

Modernization Act 2.0: https://www.congress.gov/bill/117th-congress/senate-bill/5002

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Leasure, C.S., Neuert, G. Modelling patient drug exposure profiles in vitro to narrow the valley of death. Nat Rev Bioeng 2, 196–197 (2024). https://doi.org/10.1038/s44222-024-00160-x

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s44222-024-00160-x

Search

Advanced search

Quick links

Nature Briefing: Translational Research

Sign up for the Nature Briefing: Translational Research newsletter — top stories in biotechnology, drug discovery and pharma.

Get what matters in translational research, free to your inbox weekly. Sign up for Nature Briefing: Translational Research