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CPT: pharmacometrics & systems pharmacology
07, 2022;11 (7): 805-821.

Guide to development of compound files for PBPK modeling in the Simcyp population-based simulator.

Udoamaka Ezuruike, Mian Zhang, Amita Pansari, Mailys De Sousa Mendes, Xian Pan, Sibylle Neuhoff, Iain Gardner
Author Information
  1. Udoamaka Ezuruike: Simcyp Division, Certara UK Limited, Sheffield, UK. ORCID
  2. Mian Zhang: Simcyp Division, Certara UK Limited, Sheffield, UK. ORCID
  3. Amita Pansari: Simcyp Division, Certara UK Limited, Sheffield, UK.
  4. Mailys De Sousa Mendes: Simcyp Division, Certara UK Limited, Sheffield, UK.
  5. Xian Pan: Simcyp Division, Certara UK Limited, Sheffield, UK. ORCID
  6. Sibylle Neuhoff: Simcyp Division, Certara UK Limited, Sheffield, UK. ORCID
  7. Iain Gardner: Simcyp Division, Certara UK Limited, Sheffield, UK.
PMID: 35344639 DOI: 10.1002/psp4.12791

Abstract

The Simcyp Simulator is a software platform for population physiologically-based pharmacokinetic (PBPK) modeling and simulation. It links in vitro data to in vivo absorption, distribution, metabolism, excretion and pharmacokinetic/pharmacodynamic outcomes to explore clinical scenarios and support drug development decisions, including regulatory submissions and drug labels. This tutorial describes the different input parameters required, as well as the considerations needed when developing a PBPK model within the Simulator, for a small molecule intended for oral administration. A case study showing the development and application of a PBPK model for ondansetron is herein used to aid the understanding of different PBPK model development concepts.

References

  1. J Pharm Sci. 2006 Jun;95(6):1238-57 [PMID: 16639716]
  2. Drug Metab Dispos. 1994 Mar-Apr;22(2):269-74 [PMID: 8013282]
  3. Biopharm Drug Dispos. 2017 Mar;38(2):94-114 [PMID: 28214380]
  4. Mol Pharm. 2017 Dec 4;14(12):4305-4320 [PMID: 28771009]
  5. Xenobiotica. 2007 Aug;37(8):832-54 [PMID: 17701832]
  6. Spectrochim Acta A Mol Biomol Spectrosc. 2012 Feb;86:410-6 [PMID: 22112579]
  7. J Pharm Sci. 2004 Jun;93(6):1628-40 [PMID: 15124219]
  8. Br J Clin Pharmacol. 1993 Apr;35(4):441-3 [PMID: 8485026]
  9. Clin Pharmacol Ther. 2012 Jul;92(1):17-20 [PMID: 22713733]
  10. Nat Rev Drug Discov. 2010 Dec;9(12):929-39 [PMID: 21119731]
  11. J Pharm Pharmacol. 1997 Jul;49(7):682-6 [PMID: 9255711]
  12. Drug Metab Dispos. 2016 Jun;44(6):821-32 [PMID: 27026679]
  13. Clin Ther. 2014 Feb 1;36(2):211-24 [PMID: 24486335]
  14. Clin Pharmacol Ther. 2013 Aug;94(2):260-8 [PMID: 23588308]
  15. Eur J Pharm Sci. 2011 Jun 14;43(3):160-73 [PMID: 21540107]
  16. AAPS J. 2020 Jul 17;22(5):93 [PMID: 32681207]
  17. Clin Pharmacol Ther. 2004 Oct;76(4):391 [PMID: 15470340]
  18. Pharmacogenomics J. 2012 Feb;12(1):22-9 [PMID: 20921968]
  19. J Med Chem. 1998 Dec 3;41(25):4939-49 [PMID: 9836611]
  20. Toxicol Appl Pharmacol. 2013 Nov 15;273(1):100-9 [PMID: 24001450]
  21. J Pharm Sci. 2019 Jan;108(1):21-25 [PMID: 30385284]
  22. CPT Pharmacometrics Syst Pharmacol. 2021 May;10(5):420-427 [PMID: 33793084]
  23. Nat Rev Drug Discov. 2007 Feb;6(2):140-8 [PMID: 17268485]
  24. Mol Pharm. 2020 Jul 6;17(7):2329-2344 [PMID: 32427480]
  25. Clin Pharmacol Ther. 1992 Jan;51(1):51-5 [PMID: 1531044]
  26. Clin Pharmacol Ther. 2018 Feb;103(2):224-232 [PMID: 29023678]
  27. Pharm Res. 1993 Dec;10(12):1722-5 [PMID: 8302757]
  28. Curr Drug Metab. 2007 Oct;8(7):676-84 [PMID: 17979655]
  29. CPT Pharmacometrics Syst Pharmacol. 2022 Jul;11(7):805-821 [PMID: 35344639]
  30. J Pharm Sci. 2011 Oct;100(10):4518-35 [PMID: 21710508]
  31. Clin Pharmacol Ther. 2021 Jan;109(1):51-54 [PMID: 33220063]
  32. Expert Opin Drug Metab Toxicol. 2009 Feb;5(2):211-23 [PMID: 19199378]
  33. Xenobiotica. 2006 Jun;36(6):473-97 [PMID: 16769646]
  34. Bioorg Med Chem. 2005 Aug 1;13(15):4721-32 [PMID: 15936203]
  35. AAPS J. 2011 Dec;13(4):519-47 [PMID: 21818695]
  36. J Pharm Sci. 2019 Oct;108(10):3157-3168 [PMID: 31181225]
  37. AAPS J. 2009 Jun;11(2):225-37 [PMID: 19381840]
  38. Br J Clin Pharmacol. 2021 Feb;87(2):516-526 [PMID: 32495990]
  39. Clin Pharmacokinet. 2013 Dec;52(12):1085-100 [PMID: 23818090]
  40. Clin Pharmacol Ther. 2020 May;107(5):1082-1115 [PMID: 31628859]
  41. Br J Clin Pharmacol. 1994 Apr;37(4):389-91 [PMID: 8018461]
  42. J Clin Pharmacol. 1996 Mar;36(3):206-15 [PMID: 8690814]
  43. Toxicol In Vitro. 2019 Aug;58:42-50 [PMID: 30599189]
  44. J Pharm Sci. 2013 Sep;102(9):3145-60 [PMID: 23703021]
  45. Eur J Cancer Clin Oncol. 1989;25 Suppl 1:S21-4; discussion S25-7 [PMID: 2533895]
  46. Biopharm Drug Dispos. 2021 Apr;42(4):107-117 [PMID: 33325034]
  47. Drug Metab Dispos. 2020 Feb;48(2):93-105 [PMID: 31771949]
  48. Drug Metab Dispos. 1995 Nov;23(11):1225-30 [PMID: 8591723]
  49. Clin Pharmacol Ther. 2013 Jul;94(1):64-79 [PMID: 23588311]
  50. Clin Pharmacol Ther. 1999 Apr;65(4):377-81 [PMID: 10223773]
  51. Drug Metab Dispos. 2016 Nov;44(11):1808-1818 [PMID: 27538919]
  52. J Pharm Sci. 1994 Jul;83(7):1011-3 [PMID: 7965657]
  53. Drug Metab Dispos. 2016 Apr;44(4):489-94 [PMID: 26825640]
  54. Drug Metab Dispos. 2014 Sep;42(9):1478-84 [PMID: 24989891]

MeSH Term

Administration, Oral
Computer Simulation
Humans
Models, Biological
Software
Journal Article
Article has an altmetric score of 4

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