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Sahota T, Berges A, Barton S, et al. Target Mediated Drug Disposition Model of CPHPC in Patients with Systemic Amyloidosis. CPT Pharmacometrics Syst Pharmacol. 2015;4(2):e15doi: 10.1002/psp4.15.
Sahota, T., Berges, A., Barton, S., Cookson, L., Zamuner, S., & Richards, D. (2015). Target Mediated Drug Disposition Model of CPHPC in Patients with Systemic Amyloidosis. CPT: pharmacometrics & systems pharmacology, 4(2), e15. https://doi.org/10.1002/psp4.15
Sahota, T, et al. "Target Mediated Drug Disposition Model of CPHPC in Patients with Systemic Amyloidosis." CPT: pharmacometrics & systems pharmacology vol. 4,2 (2015): e15. doi: https://doi.org/10.1002/psp4.15
Sahota T, Berges A, Barton S, Cookson L, Zamuner S, Richards D. Target Mediated Drug Disposition Model of CPHPC in Patients with Systemic Amyloidosis. CPT Pharmacometrics Syst Pharmacol. 2015 Feb;4(2):e15. doi: 10.1002/psp4.15. Epub 2015 Feb 04. PMID: 26225229; PMCID: PMC4360666.
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CPT Pharmacometrics Syst Pharmacol. 2015 Feb;4(2):e15. doi: 10.1002/psp4.15. Epub 2015 Feb 04.

Target Mediated Drug Disposition Model of CPHPC in Patients with Systemic Amyloidosis.

CPT: pharmacometrics & systems pharmacology

T Sahota, A Berges, S Barton, L Cookson, S Zamuner, D Richards

Affiliations

  1. Clinical Pharmacology Modelling and Simulation GlaxoSmithKline, UK.
  2. Clinical Statistics, GlaxoSmithKline UK.
  3. Clinical Pharmacology, Science, and Study Operations, GlaxoSmithKline UK.
  4. Academic DPU, GlaxoSmithKline UK.

PMID: 26225229 PMCID: PMC4360666 DOI: 10.1002/psp4.15

Abstract

The amyloid deposits that cause disease in systemic amyloidosis always contain the normal plasma protein, serum amyloid P (SAP) component. SAP is the target of a novel immunotherapy approach now being developed to eliminate amyloid deposits. The treatment is enabled by, and critically depends on, the use of the drug (R)-1-[6-[(R)-2-carboxy-pyrrolidin-1-yl]-6-oxo-hexanoyl]pyrrolidine-2-carboxylic acid (CPHPC, GSK2315698, Ro 63-8695), which depletes circulating SAP almost completely but leaves some SAP in amyloid deposits for specific recognition by subsequently administered therapeutic anti-SAP antibodies. Herein, we report a mechanistic model that predicts, with clinically acceptable precision, the exposure-response relationship for CPHPC, both in healthy individuals and in patients with systemic amyloidosis. The model covariates are gender, renal function, total amyloid load, and presence of hepatic amyloid, all of which are known at baseline. The model is being used to predict individualized dosing regimens in an ongoing, first-in-human study with anti-SAP antibodies.

References

  1. J Pharmacokinet Biopharm. 1998 Aug;26(4):385-408 - PubMed
  2. Nature. 2002 May 16;417(6886):254-9 - PubMed
  3. Annu Rev Med. 2006;57:223-41 - PubMed
  4. Am J Kidney Dis. 2002 Feb;39(2 Suppl 1):S1-266 - PubMed
  5. J Nucl Med. 1998 Apr;39(4):699-706 - PubMed
  6. Clin Pharmacol Ther. 1994 Sep;56(3):248-52 - PubMed
  7. Br J Haematol. 2010 Mar;148(5):760-7 - PubMed
  8. Clin Chim Acta. 1991 Aug 30;200(2-3):191-9 - PubMed
  9. Nature. 2010 Nov 4;468(7320):93-7 - PubMed
  10. Pharm Res. 2012 Mar;29(3):866-82 - PubMed
  11. J Pharmacokinet Pharmacodyn. 2014 Jun;41(3):223-38 - PubMed
  12. J Clin Invest. 1990 Dec;86(6):1862-9 - PubMed
  13. Comput Methods Programs Biomed. 2004 Aug;75(2):85-94 - PubMed
  14. Clin Exp Immunol. 1979 Nov;38(2):284-93 - PubMed
  15. CPT Pharmacometrics Syst Pharmacol. 2013 Jun 26;2:e50 - PubMed
  16. J Pharmacokinet Pharmacodyn. 2008 Oct;35(5):573-91 - PubMed
  17. Proc Natl Acad Sci U S A. 2009 May 5;106(18):7619-23 - PubMed

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