Pharmacodynamic model of hepcidin regulation of iron homeostasis in cynomolgus monkeys

AAPS Journal

Volumn 18, Issue 3, 2016, Pages 713-727

  Krzyzanski, Wojciech ^a   Xiao, Jim J ^b,c   Sasu, Barbra ^b,d   Hinkle, Beth ^b   Perez Ruixo, Juan Jose ^b,e  

^a UNIVERSITY AT BUFFALO   (United States)

^b AMGEN INC   (United States)

^c Clovis Oncology Inc   (United States)

^d PFIZER INC   (United States)

^e JANSSEN RESEARCH AND DEVELOPMENT   (Belgium)

Author keywords

Ferrokinetics; Hepcidin; Iron kinetics; Iron restricted erythropoiesis

Indexed keywords

12B9M ANTIBODY; FERROPORTIN; HEMOGLOBIN; HEPCIDIN; IRON; MONOCLONAL ANTIBODY; PLACEBO; UNCLASSIFIED DRUG; HEPCIDIN 25, HUMAN;

ANIMAL EXPERIMENT; ARTICLE; CONTROLLED STUDY; DRUG BLOOD LEVEL; DRUG MECHANISM; ERYTHROPOIESIS; FEMALE; HOMEOSTASIS; HORMONE BLOOD LEVEL; IC50; IRON BLOOD LEVEL; IRON HOMEOSTASIS; IRON TRANSPORT; LIVER; LIVER CELL; MACACA FASCICULARIS; MACROPHAGE; MALE; NONHUMAN; PREDICTION; RETICULOENDOTHELIAL MACROPHAGE; SIMULATION; SINGLE DRUG DOSE; ANIMAL; ANTAGONISTS AND INHIBITORS; BIOLOGICAL MODEL; BLOOD; DRUG EFFECTS; PHYSIOLOGY;

ANIMALS; ANTIBODIES, MONOCLONAL; HEPCIDINS; HOMEOSTASIS; IRON; MACACA FASCICULARIS; MODELS, BIOLOGICAL;

EID: 85007575453     PISSN: None     EISSN: 15507416     Source Type: Journal    
DOI: 10.1208/s12248-016-9886-1     Document Type: Article

References (33)

1. Andrews NC. Disorders of iron metabolism. N Eng J Med. 1999;341:1986-95.
2. Ganz T. Molecular control of iron transport. J Am Soc Nephrol. 2007;18:394-400.
3. Kemna E, Pickkers P, Nemeth E, van der Hoeven H, Swinkels D. Time-course analysis of hepcidin, serum iron, and plasma cytokine levels in humans injected with LPS. Blood. 2005;106:1864-6.
4. Sun CC, Vaja V, Babitt JL, Lin HY. Targeting the hepcidin-ferroportin axis to develop new treatment strategies for anemia of chronic disease and anemia of inflammation. Am J Hematol. 2012;87:392-400.
5. Cooke KS, Hinkle B, Salimi-Moosavi H, Foltz I, King C, Rathanaswami P, et al. A fully human anti-hepcidin antibody modulates iron metabolism in both mice and nonhuman primates. Blood. 2013;122:3054-61.
6. Xiao JJ, Krzyzanski W, Wang Y-M, Li H, Rose MJ, Ma M, et al. Pharmacokinetics of anti-hepcidin monoclonal antibody Ab 12B9m and hepcidin in cynomolgus monkeys. AAPS J. 2010;12:646-57.
7. McCance RA, Widdowson EM. Absorption and excretion of iron. Lancet. 1937;230:680-4.
8. Nooney GC. An erythron-dependent model of iron kinetics. Biophys J. 1966;6:601-9.
9. Ricketts C, Jacobs A, Cavill I. Ferrokinetics and erythropoiesis in man: the measurement of effective erythropoiesis, ineffective erythropoiesis and red cell lifespan using 59Fe. Br J Haematol. 1975;31:65-75.
10. Stefanelli M, Bentley DP, Cavill I, Roeser HP. Quantitation of reticuloendothelial iron kinetics in humans. Am J Physiol Regul Integr Comp Physiol. 1984;247:842-9.
11. Lopes TJS, Luganskaja T, Spasic MV, Hentze MW, Mutzkenthaler MU, Schumann K, et al. System analysis of iron metabolism: the network of iron pools and fluxes. BMC Syst Biol. 2010;4:112.
12. Hosain F, Marsaglia G, Finch CA. Blood ferrokinetics in normal man. J Clin Invest. 1967;46:1-9.
13. Cook JD, Marsaglia G, Eschbach JW, Funk DD, Finch CA. Ferrokinetics: a biologic model for plasma iron exchange in man. J Clin Invest. 1970;49:197-205.
14. Fillet G, Beguin Y, Baldelli L. Model of reticuloendothelial iron metabolismin humans: abnormal behavior in idiopathic hemo-chromatosis and inflammation. Blood. 1989;74:844-51.
15. National Research Council of the National Academies. Guide for the care and use of laboratory animals. 8th ed. Washington DC: The National Academies Press; 2011.
16. D’Argenio DZ, Schumitzky A, Wang X. ADAPT 5 user’s guide: pharmacokinetic/pharmacodynamic systems analysis software. Los Angeles: Biomedical Simulations Resource; 2009.
17. Landaw SA. Factors that accelerate or retard red blood cell senescence. Blood Cells. 1988;14:47-59.
18. Bucher NLR, Malt RA. Regeneration of liver and kidney. Boston: Little Brown; 1971.
19. Gonzalez-Mejia ME, Doseff AI. Regulation of monocytes and macrophages cell fate. Front Biosci. 2009;14:2413-31.
20. Burwell EL, Brickley BA, Finch CA. Erythrocyte life span in small animals; comparison of two methods employing radioiron. Am J Physiol. 1953;172:718-24.
21. Gaweda AE, Ginzburg YZ, Chait Y, Germain MJ, Aronoff GR, Rachmilewitz E. Iron dosing in kidney disease: inconsistency of evidence and clinical practice. Nephrol Dial Transplant. 2015;30:187-96.
22. Nathanson MH, McLaren GD. Computer simulation of iron absorption: regulation of mucosal and systemic iron kinetics in dogs. J Nutr. 1987;117:1067-75.
23. Sharma A, Ebling W, Jusko WJ. Precursor-dependent indirect pharmacodynamic response model for tolerance and rebound phenomena. J Pharm Sci. 1998;87:1577-84.
24. Ramakrishnan R, Cheung WK, Farrell F, Kelley M, Jolliffe L, Jusko WJ. Pharmacokinetic and phramacodynamic modeling of recombinant human erythropoietin after intravenous and subcutaneous single dose administrations in cynomolgus monkeys. J Pharmacol Exp Ther. 2003;306:324-31.
25. Krzyzanski W, Jusko WJ, Wacholtz MC, Minton N, Cheung WK. Pharmacokinetic and pharmacodynamic modeling of recombinant human erythropoietin after multiple subcutaneous doses in healthy subjects. Eur J Pharm Sci. 2005;26:295-306.
26. Woo S, Krzyzanski W, Jusko WJ. Pharmacokinetic and pharmacodynamic modeling of recombinant human erythropoietin after intravenous and subcutaneous administration in rats. J Pharmacol Exp Ther. 2006;319:1297-306.
27. Pérez-Ruixo JJ, Krzyzanski W, Hing J. Pharmacodynamic analysis of recombinant human erythropoietin effect on reticu-locyte production rate and age distribution in healthy subjects. Clin Pharmacokinet. 2008;47:399-415.
28. Pérez-Ruixo JJ, Krzyzanski W, Bouman-Thio E, Miller B, Jang H, Bai SA, et al. Pharmacokinetics and pharmacodynamics of the erythropoietin mimetibody construct CNTO 528 in healthy subjects. Clin Pharmacokinet. 2009;48:601-13.
29. Andrews NC. Iron deficiency and related disorders. In: Greer JP, Foerster J, Luken JN, Roders GM, Paraskevanos F, Glader B, editors. Wintrobe’s clinical hematology, vol. I. 11th ed. Philadelphia: Lippincott Williams & Wilkins; 2004.
30. Doshi S, Krzyzanski W, Yue S, Elliott S, Chow A, Pérez-Ruixo JJ. Clinical pharmacokinetics and pharmacodynamics of erythropoiesis-stimulating agents. Clin Pharmacokinet. 2013;52:1063-83.
31. Ashby DR, Gale DP, Busbridge M, Murphy KG, Duncan ND, Cairns TD, et al. Erythropoietin administration in humans causes a marked and prolonged reduction in circulating hepcidin. Haematologica. 2010;95:505-8.
32. Weiss G, Goodnough LT. Anemia of chronic disease. N Engl J Med. 2005;352:1011-23.
33. Goodnough LT, Nemeth E, Ganz T. Detection, evaluation, and management of iron-restricted erythropoiesis. Blood. 2010;116:4754-61.