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БИОпрепараты. Профилактика, диагностика, лечение

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Фармакокинетические свойства препаратов белковой природы

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Аннотация

Биологические препараты существенно отличаются от низкомолекулярных химических препаратов по молекулярной массе, многомерной структуре действующего вещества, наличием посттрансляционных модификаций, составу примесей и вспомогательных веществ, производственному процессу получения препарата и др. Данные особенности биологических препаратов оказывают влияние и на их фармакокинетические свойства. Изучение фармакокинетических свойств необходимо не только для обоснования эффективности биологического препарата, но и является ключевым исследованием для демонстрации подобия/сходства разрабатываемого биоподобного и референтного (оригинального) препаратов. Биологические препараты с высокой молекулярной массой при подкожном и внутримышечном введении из места инъекции вначале мигрируют в сосуды лимфатической системы, а затем попадают в кровь. На фармакокинетические свойства препаратов, имеющих в своем составе Fc фрагмент иммуноглобулина, оказывает влияние их способность взаимодействовать с Fcy и FcRn рецепторами. Практически все биологические препараты обладают иммуно-генностью, появление антител к препарату вызывает изменение не только фармакодинамических, но фармакокинетических свойств биологических препаратов. Оценка фармакокинетических свойств представляет собой сложный и трудоемкий процесс, например, изучение распределения препарата может потребовать в некоторых случаях использование радиоактивной метки.

Об авторах

А. А. Солдатов
Федеральное государственное бюджетное учреждение «Научный центр экспертизы средств медицинского применения» Министерства здравоохранения Российской Федерации
Россия


Ж. И. Авдеева
Федеральное государственное бюджетное учреждение «Научный центр экспертизы средств медицинского применения» Министерства здравоохранения Российской Федерации
Россия


Н. А. Алпатова
Федеральное государственное бюджетное учреждение «Научный центр экспертизы средств медицинского применения» Министерства здравоохранения Российской Федерации
Россия


Н. В. Медуницын
Федеральное государственное бюджетное учреждение «Научный центр экспертизы средств медицинского применения» Министерства здравоохранения Российской Федерации
Россия


С. Л. Лысикова
Федеральное государственное бюджетное учреждение «Научный центр экспертизы средств медицинского применения» Министерства здравоохранения Российской Федерации
Россия


В. А. Меркулов
Федеральное государственное бюджетное учреждение «Научный центр экспертизы средств медицинского применения» Министерства здравоохранения Российской Федерации
Россия


Список литературы

1. Pharmacokinetics and Pharmacodynamics of Biotech Drugs: Principles and Case Studies in Drug Development. Edited by Bernd Meibohm. WiLeY-VCH Verlag GmbH. 2006.

2. Mould D.R., Sweeney K.R.D. The pharmacokinetics and pharmacodynamics of monoclonal antibodies - mechanistic modeling applied to drug development. Current Opinion in Drug Discovery & Development 2007; 10(1): 84-96.

3. Baumann A.Early Development of TherapeuticBiologics - Pharmacokinetics. Current Drug Metabolism 2006; 7: 15-21.

4. Keizer R.J., Huitema A.D., Schellens J.H., Beijnen J.H. Clinical pharmacokinetics of therapeutic monoclonal antibodies. Clin Pharmacokinet. 2010; 49: 493-507.

5. Gibson C.R., Sandu P., Hanley W.D. Monoclonal Antibody Pharmacokinetics and Pharmacodynamics. In: An Z, editor. Monoclonal antibody pharmacokinetics and pharmacodynamics, in Therapeutic monoclonal antibodies: From bench to clinic. Hoboken, New Jersey: John Wiley & Son Inc.; 2009.

6. McDonald T.A., Zepeda M.L., Tomlinson M.J., Bee W.H., Ivens I.A. Subcutaneous administration of biotherapeutics: current experience in animal models. Curr Opin Mol Ther. 2010; 12: 461-470.

7. Beshyah S.A., Anyaoku V., Niththyananthan R., Sharp P., Johnston D.G. The effect of subcutaneous injection site on absorption of human growth hormone: abdomen versus thigh. Clin Endocrinol. 1991; 35: 409-412.

8. Kagan L., Gershkovich P., Mendelman A., Amsili S., Ezov N., Hoffman A. The role of the lymphatic system in subcutaneous absorption of macromolecules in the rat model. Eur J Pharm Biopharm. 2007; 67: 759-765.

9. Kagan L., Turner M.R., Balu-Iyer S.V., Mager D.E. Subcutaneous absorption of monoclonal antibodies: role of dose, site of injection, and injection volume on rituximab pharmacokinetics in rats. Pharm Res. 2012; 29: 490-499.

10. Lin J.H. Pharmacokinetics of biotech drugs: peptides, proteins and monoclonal antibodies. Curr Drug Metab. 2009; 10: 661-691.

11. Xiao J.J. Pharmacokinetic Models for FcRn-Mediated IgG Disposition. Journal of Biomedicine and Biotechnology 2012; 2: 1-13.

12. Kurzrock R., Rosenblum M.G., Sherwin S.A. et al. Pharmacokinetics, singledose tolerance, and biological activity of recombinant gammainterferon in cancer patients. Cancer Res. 1985; 45: 2866-2872.

13. Radwanski E., Perentesis G., Jacobs S. et al. Pharmacokinetics of interferon a-2b in healthy volunteers. J Clin Pharmacol. 1987; 27: 432-435.

14. McLennan D.N., Christopher J.H., Porter E. et al. Lymphatic absorption is the primary contributor to the systemic availability of epoetin alfa following subcutaneous administration to sheep. J Pharmacol Experim Therapeut. 2004; 313: 345-351.

15. Vugmeyster Y., DeFranco D., Szklut P., Wang Q., Xu X. Biodistribution of [125I]-labeled therapeutic proteins: application in protein drug development beyond oncology. J Pharm Sci. 2010; 99: 1028-1045.

16. Dong J.Q., Salinger D.H., Endres C.J., Gibbs J.P. et. al. Quantitative prediction of human pharmacokinetics for monoclonal antibodies: retrospective analysis of monkey as a single species for first-in-human prediction. Clin Pharmacokinet. 2011; 50: 131-142.

17. Kagan L., Turner M.R., Balu-Iyer S.V., Mager D.E. Subcutaneous absorption of monoclonal antibodies: role of dose, site of injection, and injection volume on rituximab pharmacokinetics in rats. Pharm Res. 2012; 29: 490-499.

18. Zapf J., Hauri C., Waldvogel M. et al. Acute metabolic effects and half-lives of intravenously administered insulinlike growth factors I and II in normal and hypophysectomizedrats. J Clin Invest. 1986; 77: 1768-1775.

19. Charman S.A., Segrave A.M., Edwards G.A., Porter C.J. Systemic availability and lymphatic transport of human growth hormone administered by subcutaneous injection. J Pharm Sci. 2000; 89: 168-177.

20. Richter W.F., Bhansali S.G., Morris M.E. Mechanistic Determinants of Biotherapeutics Absorption Following SC Administration. The AAPS Journal, 2012; 14(3): 559-570.

21. Bocci V., Muscettola M., Grasso G., Magyar Z. et al. The lymphatic route. 1) Albumin and hyaluronidase modify the normal distribution of interferon in lymph and plasma. Experientia 1986; 42: 432-433.

22. Mannucci P.M., Kempton C., Millar C., Romond E. et al. Pharmacokinetics and safety of a novel recombinant human von Willebrand factor manufactured with a plasma-free method: a prospective clinical trial. Blood 2013; 122(5): 648-657.

23. Agerso H., Laesen L.S., Riis A. et al. Pharmacokinetics and renal excretion of desmopressin after intravenous administration to healthy subjects and renally impaired patients. Br J Clin Pharmacol. 2004; 58: 352-358.

24. Kovarki J.M., Kahan B.D., Rajagopalan P.R. et al. Population pharmacokinetics and exposure-response relationships for basiliximab in kidney transplantation. Transplant. 1999; 68: 1288-94.

25. Berrettini M., Mariani G., Schiavoni M. et al. Pharmacokinetic evaluation of recombinant, activated factor VII in patients with inherited factor VII deficiency Haematologica 2001; 86(6): 640-45.

26. Krippendorff B.F., Kuester K., Kloft C., Huisinga W. Nonlinear pharmacokinetics of therapeutic proteins resulting from receptor mediated endocytosis. J Pharmacokinet Pharmacodyn. 2009; 36: 239-260.

27. Xu X., Vugmeyster Y. Challenges and Opportunities in Absorption, Distribution, Metabolism, and Excretion Studies of Therapeutic Biologics. The AAPS Journal 2012; 14(4): 781-882.

28. Wang W., Wang E.Q., Balthasar J.P. Monoclonal Antibody Pharmacokinetics and Pharmacodynamics. Clin. Pharmacology & Therapeutics 2008; 84(5): 548-558.

29. Insulin inhalation-Pfizer / Nektar therapeutic: HMR 4006, inhaled PEGinsulin-Nektar, PEGylated insurin-Nektar. Drugs R.D. 2004; 5: 166-170.

30. Baumann A. Early Development of TherapeuticBiologics - Pharmacokinetics. Current Drug Metabolism 2006; 7: 15-21.

31. Fracasso P.M., Burris H., Arquette M.A., Govindan R. et al. A phase 1 escalating single-dose and weekly fixed-dose study of cetuximab: pharmacokinetic and pharmacodynamic rationale for dosing. Clin Cancer Res. 2007; 13: 986-993.

32. Urva S.R., Balthasar J.P. Target mediated disposition of T84.66, a monoclonal anti-CEA antibody: application in the detection of colorectal cancer xenografts. MAbs. 2010; 2: 67-72.

33. Vugmeyster Y., Szklut P., Wensel D., Ross J. et al. Complex pharmacokinetics of a humanized antibody against human amyloid beta peptide, anti-abeta Ab2, in nonclinical species. Pharm Res. 2011; 28: 1696-1706.

34. Gibiansky L., Gibiansky E. Target-mediated drug disposition model: relationships with indirect response models and application to population PK-PD analysis. J Pharmacokinet Pharmacodyn. 2009; 36: 341-351.

35. Gibiansky L., Gibiansky E. Target-mediated drug disposition model: approximations, identifiability of model parameters and applications to the population pharmacokinetic-pharmacodynamic modeling of biologics. Expert Opin Drug Metab Toxicol. 2009; 5: 803-812.

36. Kuter D.J., Rosenberg RD. The reciprocal relationship of thrombopoietin (c-Mpl ligand) to changes in the platelet mass during busulfan-induced thrombocytopenia in the rabbit. Blood 1995; 85: 2720-30.

37. Kurschner C., Ozmen L., Garotta G. et al. IFN-gamma receptor-Ig fusion proteins: Half-life, immunogenicity, and in vivo activity. J Immunol. 1992; 149: 4096-100.

38. Teng M.N., Turksen K., Jacobs C.A. et al. Prevention of runting and cachexia by a chimeric TN F receptor-Fc protein. Clin Immunol Immunopathol. 1993; 69: 215-222.

39. Sato T.A., Widmer M.B., Finkelman F.D. et al. Recombinant soluble murine IL-4 receptor can inhibit or enhance Ig Eresponses in vivo. J Immunol. 1993; 150: 2717-23.

40. Finkelman F.D., Madden K.B., Morris S.C. et al. Anti-cytokine antibodies as carrier proteins. Prolongation of in vivo effects of exogenous cytokines by injection of cytokine-anti-cytokine antibody complexes. J Immunol. 1993; 151: 1235-44.

41. Schobitz B., Pezeshki G,. Pohl T. et al. Soluble interleukin-6 (IL-6) receptor augments central effects of IL-6 in vivo. Faseb J. 1995; 9: 659-64.

42. Aderka D., Engelmann H., Maor Y. et al. Stabilization of the bioactivity of tumor necrosis factor by its soluble receptors. J Exp Med. 1992; 175: 323-329.

43. Baumann G., Shaw M.A., Amburn K. Circulating growth hormone binding proteins. J Endocrinol Invest. 1994; 17: 67-81.

44. Baumann G., Vance M.L., Shaw M.A. et al. Plasma transport of human growth hormone in vivo. J Clin Endocrinol Metab. 1990; 71: 470-73.

45. Baumann G., Shaw M.A., Brumbaugh R.C. et al. Short stature and decreased serum growth hormone-binding protein in the Mountain Ok people of Papua New Guinea. J Clin Endocrinol Metab. 1991; 72: 1346-9.

46. Svenson M., Geborek P., Saxne T., Bendtzen K. Monitoring patients treated with anti-TNF-alpha biopharmaceuticals: assessing serum infliximab and antiinfliximab antibodies. Rheumatology 2007; 46: 1828-34.

47. Stephens S., Emtage S., Vetterlein O. et al. Comprehensive pharmacokinetics of a humanized antibody and analysis of residual anti-idiotypic responses. Immunology 1995; 85: 668-74.

48. Yver A., Homery M.C., Fuseau E. et al. Pharmacokinetics and safety of roledumab, a novel human recombinant monoclonal anti-RhD antibody with an optimized Fc for improved engagement of FCcRIII, in healthy volunteers. Vox Sanguinis 2012; 103: 213-22.

49. Kuo T.T., Baker K., Yoshida M. et al. Neonatal Fc receptor: from immunity to therapeutics. J Clin Immunol. 2010; 30: 777-89.

50. Roopenian D.C., Sun V.Z. Clinical ramifications of the MHC family Fc receptor FcRn. J Clin Immunol. 2010; 30: 790-97.

51. Ghetie V., Ward E.S. Multiple roles for the major histocompatibility complex class I- related receptor FcRn. Annu Rev Immunol. 2000; 18: 739-66.

52. Petkova S.B., Akilesh S., Sproule T.J. et al. Enhanced half-life of genetically engineered human IgG1 antibodies in a humanized FcRn mouse model: potential application in humorally mediated autoimmune disease. Int Immunol. 2006; 18(12): 1759-69.

53. Jaggi J.S., Carrasquillo J.A., Seshan S.V. et al. Improved tumor imaging and therapy via i.v. IgG-mediated time-sequential modulation of neonatal Fc receptor. J Clin Invest. 2007; 117(9): 2422-30.

54. Zhou J., Johnson J.E., Ghetie V. et al. Generation of mutated variants of the human form of the MHC class I-related receptor, FcRn, with increased affinity for mouse immunoglobulin G. J Mol Biol. 2003; 332(4): 901-13.

55. Deng R., Loyet K.M., Lien S., Iyer S. et al. Pharmacokinetics of humanized monoclonal anti-tumor necrosis factor-{alpha} antibody and its neonatal Fc receptor variants in mice and cynomolgus monkeys. Drug Metab Dispos. 2010; 38: 600-05.

56. Dall’Acqua W.F., Kiener P.A., Wu H. Properties of human IgG1s engineered for enhanced binding to the neonatal Fc receptor (FcRn). J Biol Chem. 2006; 281: 23514-24.

57. Yeung Y.A., Leabman M.K., Marvin J.S., Qiu J. et al. Engineering human IgG1 affinity to human neonatal Fc receptor: impact of affinity improvement on pharmacokinetics in primates. J Immunol. 2009; 182: 7663-71.

58. Sarav M., Wang Y., Hack B.K. et al. Renal FcRn Reclaims Albumin but Facilitates Elimination of IgG. J Am Soc Nephrol. 2009; 20(9): 1941-52.

59. Kaneko E., Niwa R. Optimizing therapeutic antibody function: progress with Fc domain engineering. BioDrugs 2011; 25: 1-11.

60. Shinkawa T., Nakamura K., Yamane N., Shoji-Hosaka E. et al. The absence of fucose but not the presence of galactose or bisecting N-acetylglucosamine of human IgG1 complex-type oligosaccharides shows the critical role of enhancing antibody-dependent cellular cytotoxicity J Biol Chem. 2003; 278: 3466-73.

61. Hodoniczky J., Zheng Y.Z., James D.C. Control of recombinant monoclonal antibody effector functions by Fc N-glycan remodeling in vitro. Biotechnol Prog. 2005; 21: 1644-52.

62. Gregoriadis G., Fernandes A., Mital M., McCormack B. Polysialic acids: potential in improving the stability and pharmacokinetics of proteins and other therapeutics. Cell Mol Life Sci. 2000; 57: 1964-69.

63. Bailon P., Won C.Y. PEG-modified biopharmaceuticals. Expert Opin Drug Deliv. 2009; 6: 1-16.

64. Boswell C.A., Tesar D.B., Mukhyala K., Theil F.P. et al. Effects of charge on antibody tissue distribution and pharmacokinetics. Bioconjug Chem. 2010; 21: 2153-63.

65. Schifferli J.A., Taylor R.P. Physiological and pathological aspects of circulating immune complexes. Kidney Int. 1989; 35: 993-1003.

66. Emlen W., Carl V., Burdick G. Mechanism of transfer of immune complexes from red blood cell CR1 to monocytes. Clin Exp Immunol. 1992; 89: 8-17.

67. Johansson A., Erlandsson A., Eriksson D., Ullén A. et al. Idiotypic-anti-idiotypic complexes and their in vivo metabolism. Cancer 2002; 94: 1306-13.

68. Kosugi I., Muro H., Shirasawa H., Ito I. Endocytosis of soluble IgG immune complex and its transport to lysosomes in hepatic sinusoidal endothelial cells. J Hepatol. 1992; 16: 106-14.

69. Pastuskovas C.V., Mallet W., Clark S., Kenrick M. et al. Effect of immune complex formation on the distribution of a novel antibody to the ovarian tumor antigen CA125. Drug Metab Dispos. 2010; 38: 2309-19.

70. Tabrizi M.T., Tseng C.M.L., Roskos L.K. Elimination mechanisms of therapeutic monoclonal antibodies. Drug Discov Today 2006; 11: 81-88.

71. Pollock C., Johnson D.W., Hörl W.H., Rossert J. et al. Pure red cell aplasia induced by erythropoiesis-stimulating agents. Clin J Am Soc Nephrol. 2008; 3: 193-99.

72. Rossert J. Erythropoietin-induced, antibody-mediated pure red cell aplasia. Eur J Clin Invest. 2005; 35(Suppl 3): 95-99.

73. Wight J., Paisley S. The epidemiology of inhibitors in haemophilia A: a systematic review. Haemophilia 2003; 9: 418-35.

74. Guidelines on the quality, safety, and efficacy of biotherapeutic protein products prepared by recombinant DNA technology. Replacement of Annex

75. of WHO Technical Report Series, № 814.

76. Guideline on the clinical investigation of the pharmacokinetics of therapeutic proteins (CHMP/EWP/89249/2004).

77. Vugmeyster Y., Szklut P., Wensel D., Ross J., Xu X., Awwad M., Gill D., Tchistiakov L., Warner G. Complex pharmacokinetics of a humanized antibody against human amyloid beta peptide, anti-abeta Ab2, in nonclinical species. Pharm Res. 2011; 28: 1696-1706.

78. Bumbaca D., Wong A., Drake E., Reyes A.E., Lin B.C. et al. Highly specific offtarget binding identified and eliminated during the humanization of an antibody against FGF receptor 4. MAbs. 2011; 3: 376-86.

79. Guideline on the clinical investigation of recombinant and human plasma-derived factor VIII products. EMA/CHMP/BPWP/144533/2009.

80. Guideline on clinical investigation of recombinant and human plasma-derived factor IX products. EMA/CHMP/BPWP/144552/2009.

81. Guideline on comparability of biotechnology-derived medicinal products after a change in the manufacturing process. Non-clinical and clinical issues. EMEA/CHMP/BMWP/101695/2006.

82. Similar biological medicinal products containing biotechnology-derived proteins as active substance: non-clinical and clinical issues. EMEA/CHMP/ BMWP/42832/2005.

83. Heinemann L., Hompesch M. Biosimilar Insulins: How Similar is Similar? Journal of Diabetes Science and Technology 2011; 5(3): 741-55.


Для цитирования:


Солдатов А.А., Авдеева Ж.И., Алпатова Н.А., Медуницын Н.В., Лысикова С.Л., Меркулов В.А. Фармакокинетические свойства препаратов белковой природы. БИОпрепараты. Профилактика, диагностика, лечение. 2015;(2):24-35.

For citation:


Soldatov A.A., Avdeeva Z.I., Alpatova N.A., Medunitsyn N.V., Lysikova S.L., Merkulov V.A. Pharmacokinetic properties of the preparations of protein origin. BIOpreparations. Prevention, Diagnosis, Treatment. 2015;(2):24-35. (In Russ.)

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