Skip to main content
Log in

Predicting Human Pharmacokinetics: Physiologically Based Pharmacokinetic Modeling and In Silico ADME Prediction in Early Drug Discovery

  • Commentary
  • Published:
European Journal of Drug Metabolism and Pharmacokinetics Aims and scope Submit manuscript

The Original Article was published on 23 July 2018

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

References

  1. Waring MJ, Arrowsmith J, Leach AR, Leeson PD, Mandrell S, Owen RM, et al. An analysis of the attrition of drug candidates from four major pharmaceutical companies. Nat Rev Drug Discov. 2015;14(7):475–86.

    Article  CAS  PubMed  Google Scholar 

  2. Zhao P, Zhang L, Grillo JA, Liu Q, Bullock JM, Moon YJ, et al. Applications of physiologically based pharmacokinetic (PBPK) modeling and simulation during regulatory review. Clin Pharmacol Ther. 2011;89(2):259–67.

    Article  CAS  Google Scholar 

  3. Tsamandouras N, Rostami-Hodjegan A, Aarons L. Combining the ‘bottom up’ and ‘top down’ approaches in pharmacokinetic modelling: fitting PBPK models to observed clinical data. Br J Clin Pharmacol. 2015;79(1):48–55.

    Article  CAS  PubMed  Google Scholar 

  4. Jones HM, Chen Y, Gibson C, Heimbach T, Parrott N, Peters SA, et al. Physiologically based pharmacokinetic modeling in drug discovery and development: a pharmaceutical industry perspective. Clin Pharmacol Ther. 2015;97(3):247–62.

    Article  CAS  PubMed  Google Scholar 

  5. Rowland M, Peck C, Tucker G. Physiologically-based pharmacokinetics in drug development and regulatory science. Annu Rev Pharmacol Toxicol. 2011;51:45–73.

    Article  CAS  PubMed  Google Scholar 

  6. Jones H, Rowland-Yeo K. Basic concepts in physiologically based pharmacokinetic modeling in drug discovery and development. CPT Pharmacomet Syst Pharmacol. 2013;2:e63.

    Article  CAS  Google Scholar 

  7. Rostami-Hodjegan A. Physiologically based pharmacokinetics joined with in vitro-in vivo extrapolation of ADME: a marriage under the arch of systems pharmacology. Clin Pharmacol Ther. 2012;92(1):50–61.

    Article  CAS  PubMed  Google Scholar 

  8. Jones HM, Dickins M, Youdim K, Gosset JR, Attkins NJ, Hay TL, et al. Application of PBPK modelling in drug discovery and development at Pfizer. Xenobiotica Fate Foreign Compd Biol Syst. 2012;42(1):94–106.

    Article  CAS  Google Scholar 

  9. Jones HM, Gardner IB, Watson KJ. Modelling and PBPK simulation in drug discovery. AAPS J. 2009;11(1):155–66.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Ren HC, Sai Y, Chen T. Evaluation of generic methods to predict human pharmacokinetics using physiologically based pharmacokinetic model for early drug discovery of tyrosine kinase inhibitors. Eur J Drug Metab Pharmacokinet. 2018. https://doi.org/10.1007/s13318-018-0496-4.

    Article  Google Scholar 

  11. Chen Y, Jin JY, Mukadam S, Malhi V, Kenny JR. Application of IVIVE and PBPK modeling in prospective prediction of clinical pharmacokinetics: strategy and approach during the drug discovery phase with four case studies. Biopharm Drug Dispos. 2012;33(2):85–98.

    Article  CAS  PubMed  Google Scholar 

  12. International Transporter C, Giacomini KM, Huang SM, Tweedie DJ, Benet LZ, Brouwer KL, et al. Membrane transporters in drug development. Nat Rev Drug Discov. 2010;9(3):215–36.

    Article  CAS  Google Scholar 

  13. van de Waterbeemd H, Gifford E. ADMET in silico modelling: towards prediction paradise? Nat Rev Drug Discov. 2003;2(3):192–204.

    Article  Google Scholar 

  14. Moroy G, Martiny VY, Vayer P, Villoutreix BO, Miteva MA. Toward in silico structure-based ADMET prediction in drug discovery. Drug Discov Today. 2012;17(1–2):44–55.

    Article  CAS  PubMed  Google Scholar 

  15. Hou T, Wang J, Zhang W, Xu X. ADME evaluation in drug discovery. 6. Can oral bioavailability in humans be effectively predicted by simple molecular property-based rules? J Chem Inf Model. 2007;47(2):460–3.

    Article  CAS  PubMed  Google Scholar 

  16. Khan MT. Predictions of the ADMET properties of candidate drug molecules utilizing different QSAR/QSPR modelling approaches. Curr Drug Metab. 2010;11(4):285–95.

    Article  CAS  PubMed  Google Scholar 

  17. Winiwarter S, Ahlberg E, Watson E, Oprisiu I, Mogemark M, Noeske T, et al. In silico ADME in drug design—enhancing the impact. ADMET DMPK. 2018;6(1):15–33.

    Article  Google Scholar 

  18. Daga PR, Bolger MB, Haworth IS, Clark RD, Martin EJ. Physiologically based pharmacokinetic modeling in lead optimization. 1. Evaluation and adaptation of gastroplus to predict bioavailability of medchem series. Mol Pharm. 2018;15(3):821–30.

    Article  CAS  PubMed  Google Scholar 

  19. Poulin P, Jones RD, Jones HM, Gibson CR, Rowland M, Chien JY, et al. PHRMA CPCDC initiative on predictive models of human pharmacokinetics, part 5: prediction of plasma concentration-time profiles in human by using the physiologically-based pharmacokinetic modeling approach. J Pharm Sci. 2011;100(10):4127–57.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding authors

Correspondence to Jian Shi or Weibin Zha.

Ethics declarations

Funding

No funding was used to prepare this manuscript.

Conflict of Interest

The authors have declared no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Shi, J., Zha, W. Predicting Human Pharmacokinetics: Physiologically Based Pharmacokinetic Modeling and In Silico ADME Prediction in Early Drug Discovery. Eur J Drug Metab Pharmacokinet 44, 135–137 (2019). https://doi.org/10.1007/s13318-018-0503-9

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13318-018-0503-9

Navigation