The Use of Biotechnological Drugs in Pediatrics on the Example of Monoclonal Antibodies: Clinical Pharmacology View
https://doi.org/10.15690/pf.v18i4.2293
Abstract
The article reviews monoclonal antibodies, its structure, classifications, pharmacodynamics, pharmacokinetics, and adverse effects. There are examples for each section. Approaches to the research and criteria for drug selection in paediatrics are discussed in detail: the role of clinical trials, extrapolation and pharmacometrics. It has been shown that the differences in the pharmacokinetics of monoclonal antibodies between adults and children present due to the age-related characteristics of various physiological processes. The authors analyse such parameters as absorption, bioavailability, distribution, and elimination. The role of monoclonal antibodies immunogenicity in the structure of adverse effects in children is fully presented. Pharmacometrics is reviewed in the form of modelling and simulation in monoclonal antibodies dosing in paediatrics. It is important to consider the growth and development as “moving targets" in pediatrics regardless the principle of monoclonal antibodies dosage in children. The conclusions were made, and the guidelines were prepared based on the article results.
Supporting agencies: Not specified
About the Authors
Alexey S. Kolbin
Pavlov First Saint Petersburg State Medical University; Saint Petersburg State University
Russian Federation
Disclosure of interest:
Russian Federation
MD, PhD, Professor
6/8 Lva Tolstogo Str., St. Petersburg, 197089; +7 (921) 759-04-49; eLibrary SPIN: 7966-0845
Disclosure of interest:
Not declared
Liudmila I. Yemelyanova
Pavlov First Saint Petersburg State Medical University
Russian Federation
Disclosure of interest:
Russian Federation
6/8 Lva Tolstogo Str., St. Petersburg, 197089; +7 (921) 759-04-49
Disclosure of interest:
Not declared
References
1. Lalonde RL, Honig P. Clinical pharmacology in the era of biotherapeutics. Clin Pharmacol Ther. 2008;84(5):533-536. doi: 10.1038/clpt.2008.182
2. Federal Law of the Russian Federation dated April 12, 2010 N 61-ФЗ “Ob obrashchenii lekarstvennykh sredstv” (as amended on July 03, 2016 as amended and supplemented, entered into force on January 01, 2017). (In Russ).
3. Darrow JJ. FDA Approval and Regulation of Pharmaceuticals, 1983-2018. JAMA. 2020;323(2):164-176. doi:10.1001/jama.2019.20
4. Totolyan AA, Freidlin IS. Kletki immunnoi sistemy: Tutorial. St. Petersburg: Nauka; 2000. 231 p. (In Russ).
5. Bourne T, Fossati G, Nesbitt A. A PEGylated Fab' fragment against tumor necrosis factor for the treatment of Crohn disease: exploring a new mechanism of action. BioDrugs. 2008;22(5):331-337. doi: 10.2165/00063030-200822050-00005
6. Biologicheskie preparaty. Terapevticheskie monoklonal’nye antitela s pozitsii klinicheskoi farmakologii. Kolbin AS, ed. St. Petersburg: TsOP “Professiya”; 2019. 80 p. (In Russ).
7. Porter RR. Structural studies of immunoglobulins. Science. 1973;180(4087):713-716. doi: 10.1126/science.180.4087.713
8. Edelman GM. Antibody structure and molecular immunology. Science. 1973;180(4088):830-840. doi: 10.1126/sci-ence.180.4088.830
9. Voss JE. Engineered single-domain antibodies tackle COVID variants. Nature. 2021;595(7866):176-178. doi: 10.1038/d41586-021-01721-5
10. Budchanov YuI. Monoklonal’nye antitela. Ispol’zovanie v diagnostike zabolevanii i lechebnye monoklonal’nye antitela: Guidelines. Tver'; 2012. 22 p. (In Russ).
11. Dostalek M, Gardner I, Gurbaxani B, et al. Pharmacokinetics, pharmacodynamics and physiologically-based pharmacokinetic modelling of monoclonal antibodies. Clin Pharmacokinet. 2013;52(2):83-124. doi: 10.1007/s40262-012-0027-4
12. Morrison C. Nanobody approval gives domain antibodies a boost. Nat Rev Drug Discov. 2019;18(7):485-487. doi: 10.1038/d41573-019-00104-w
13. Wong H., Chow TW. Physiologically Based Pharmacokinetic Modeling of Therapeutic Proteins. J Pharm Sci. 2017;106(9):2270-2275. doi: 10.1016/j.xphs.2017.03.038
14. Mazurov VI, Trofimov EA. Innovative Methods of Some Systemic Autoimmune Diseases Treatment. Vestnik Rossiiskoi Akademii Meditsinskikh Nauk = Annals of the Russian Academy of Medical Sciences. 2015;70(2):165-168. (In Russ). doi: 10.15690/vramn.v70i2.1309
15. Lila AM, Nasonov EL, Olyunin JA, Galushko EA. Actual aspects of modern rheumatology. Therapy. 2018;4(4):10-17. (In Russ).
16. State Register of Medicines. (In Russ). Доступно по: http://grls. rosminzdrav.ru. Ссылка активна на 29.07.2021.
17. Nasonov EL, Lila AM. Inhibition of interleukin 6 in immune inflammatory rheumatic diseases: achievements, prospects, and hopes. Nauchno-Prakticheskaya Revmatologiya = Rheumatology Science and Practice. 2017;55(6):590-599. (In Russ). doi: 10.14412/1995-4484-2017-590-599
18. ACTEMRA® (tocilizumab) injection, for intravenous or subcutaneous use: Highlights of prescribing information. 2021. p. 49. Available online: https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/125472s044lbl.pdf#page=49. Accessed on September 29, 2021.
19. Chau CH, Steeg PS, Figg WD. Antibody-drug conjugates for cancer. Lancet. 2019;394(10200):793-804. doi: 10.1016/S0140-6736(19)31774-X
20. Kersh AE, Ng S, Chang YM, et al. Targeted Therapies: Immunologic Effects and Potential Applications Outside of Cancer. J Clin Pharmacol. 2018;58(1):7-24. doi: 10.1002/jcph.1028
21. Martins JP Kennedy PJ, Santos HA, et al. A comprehensive review of the neonatal Fc receptor and its application in drug delivery. Pharmacol Ther. 2016;161:22-39. doi: 10.1016/j.pharmthera.2016.03.007
22. Wang W, Wang EQ, Balthasar JP. Monoclonal antibody pharmacokinetics and pharmacodynamics. Clin Pharmacol Ther. 2008;84(5):548-558. doi: 10.1038/clpt.2008.170
23. Haller CA, Cosenza ME, SullivanJT. Safety issues specific to clinical development of protein therapeutics. Clin Pharmacol Ther. 2008;84(5):624-627. doi: 10.1038/clpt.2008.158.
24. Wiseman GA, Kornmeh E, Leigh B, et al. Radiation dosimetry results and safety correlations from 90Y-ibritumomab tiuxetan radioimmunotherapy for relapsed or refractory non-Hodgkin's lymphoma: combined data from 4 clinical trials. J Nucl Med. 2003;44(3):465-474.
25. Chichasova NV, Nasonov EL. Safety of using genetic engineering biological agents in rheumatoid arthritis. Sovremennaya revmatologiya = Modern Rheumatology Journal. 2010;1(10):46-58. (In Russ).
26. Cook J, Weiner D, Powell J. Regarding Combined Pediatric and Adult Trials Submitted to the US Food and Drug Administration 2012-2018. din Pharmacol Ther. 2021;109(5):1181. doi: 10.1002/cpt.2076
27. Kolbin AS. Klinicheskaya farmakologiya dlya pediatrov: Tutorial. Moscow: GEOTAR-Media; 2020. 288 p. (In Russ).
28. Sun H, Temeck JW, Chambers W, et al. Extrapolation of Efficacy in Pediatric Drug Development and Evidence-based Medicine: Progress and Lessons Learned. Ther Innov Regul Sci. 2017;2017:1-7. doi: 10.1177/2168479017725558
29. Baranov AA. Rossiiskii natsional’nyi pediatricheskii formulyar. Baranov AA, ed. Moscow: GEOTAR-Media; 2009. 912 p. (In Russ).
30. Namazova-Baranova LS, Vishneva ЕА, Dobrynina ЕА, et al. Assessing the Quality of Life Using the Health Utilities Index Questionnaire in Children With Severe Persistent Asthma During the Treatment With Omalizumab. Pediatricheskaya farmakologiya — Pediatric pharmacology. 2017;14(5): 356-365. (In Russ). doi: 10.15690/pf.v14i5.1783
31. Karachunskiy AI, Rumyantseva YuV, fon Shtakelberg A. Anti-CD19 monoclonal antibodies in acute lymphoblastic leukemia in children. Russian Journal of Pediatric Hematology аnd Oncology. 2016;3(4):60-72. (In Russ). doi: 10.17650/2311-1267-2016-3-4-60-72
32. Alekseeva EI, Bzarova TM, Fetisova AN, et al. Efficacy of etanercept treatment as a second TNF a inhibitor in patients with juvenile idiopathic arthritis and primary and secondary inefficiency or intolerance of infliximab. Voprosy sovremennoi pediatrii — Current Pediatrics. 2012;11(6):32-41. (In Russ). doi: 10.15690/vsp.v11i4.363
33. Edlund H, Melin J, Parra-Guillen ZP, Kloft C. Pharmacokinetics and pharmacokinetic-pharmacodynamic relationships of monoclonal antibodies in children. Clin Pharmacokinet. 2015;54(1):35-80. doi: 10.1007/s40262-014-0208-4
34. Liu XI, Dallmann A, Wang Y-M, et al. Monoclonal Antibodies and Fc-Fusion Proteins for Pediatric Use: Dosing, Immunogenicity, and Modeling and Simulation in Data Submitted to the US Food and Drug Administration. J Clin Pharmacol. 2019;59(8):1130-1143. doi: 10.1002/jcph.1406
35. Zhao L, Ji P, Li Z, et al. The antibody drug absorption following subcutaneous or intramuscular administration and its mathematical description by coupling physiologically based absorption process with the conventional compartment pharmacokinetic model. J Clin Pharmacol. 2013;53(3):314-325. doi: 10.1002/jcph.4
36. Ryman JT, Meibohm B. Pharmacokinetics of monoclonal antibodies. CPT Pharmacometrics Syst Pharmacol. 2017;6(9):576-588. doi: 10.1002/psp4.12224
37. Shah DK, Betts AM. Towards a platform PBPK model to characterize the plasma and tissue disposition of monoclonal antibodies in preclinical species and human. J Pharmacokinet Pharmacodyn. 2012;39(1):67-86. doi: 10.1007/s10928-011-9232-2
38. Robbie GJ, Zhao L, Mondick J, et al. Population pharmacokinetics of palivizumab, a humanized anti-respiratory syncytial virus monoclonal antibody, in adults and children. Antimicrob Agents Chemother. 2012;56(9):4927-4936. doi: 10.1128/AAC.06446-11
39. Ternant D, Paintaud G, Trachtman H, et al. A possible influence of age on absorption and elimination of adalimumab in focal segmental glomerulosclerosis (FSGS). Eur J Clin Pharmacol. 2016;72(2):253-255. doi: 10.1007/s00228-015-1973-1
40. Ku LC, Smith PB. Dosing in neonates: Special considerations in physiology and trial design. Pediatr Res. 2015;77(1-1):2-9. doi: 10.1038/pr.2014.143
41. Bellini C, Boccardo F, Bonioli E, Campisi C. Lymphodynamics in the fetus and newborn. Lymphology. 2006;39(3):110-117.
42. Malik P Edginton A. Pediatric physiology in relation to the pharmacokinetics of monoclonal antibodies. Expert Opin Drug Metab Toxicol. 2018;14(6):585-599. doi: 10.1080/17425255.2018.1482278
43. Edginton AN, Schmitt W, Willmann S. Development and evaluation of a generic physiologically based pharmacokinetic model for children. Clin Pharmacokinet. 2006;45(10):1013-1034. doi: 10.2165/00003088-200645100-00005
44. Sarin H. Physiologic upper limits of pore size of different blood capillary types and another perspective on the dual pore theory of microvascular permeability. J Angiogenes Res. 2010;2:14. doi: 10.1186/2040-2384-2-14
45. Heymann MA, Iwamoto HS, Rudolph AM. Factors affecting changes in the neonatal systemic circulation. Annu Rev Physiol. 1981;43: 371-383. doi: 10.1146/annurev.ph.43.030181.002103
46. Tassani P Schad H, Schreiber C, et al. Extravasation of albumin after cardiopulmonary bypass in newborns. J Cardiothorac Vasc Anesth. 2007;21(2):174-178. doi: 10.1053/j.jvca.2006.01.010
47. Malik PRV, Hamadeh A, Phipps C, et al. Population PBPK modelling of trastuzumab: a framework for quantifying and predicting inter-individual variability. J Pharmacokinet Pharmacodyn. 2017;44(3):277-290. doi: 10.1007/s10928-017-9515-3
48. Parving HH, Klebe JG, Ingomar CJ. Simultaneous determination of plasma volume and transcapillary escape rate with 131 I-labelled albumin and T-1824 in the newborn. Acta Paediatr Scand. 1973;62(3):248-252. doi: 10.1111/j.1651-2227.1973.tb08100.x
49. Battistini N, Virgili F, Severi S, et al. Relative expansion of extracellular water in obese vs. normal children. J Appl Physiol. 1995;79(1):94-96. doi: 10.1152/jappl.1995.79.1.94
50. Shabalov N.P Neonatologiya: Tutorial: in 2 vol. 7-e ed., revised and supplemented. Moscow: GEOTAR-Media; 2020. Vol. 2. 752 p. (In Russ).
51. Touwslager RN, Houben AJ, Tan FE, et al. Growth and endothelial function in the first 2 years of life. J Pediatr. 2015;166(3):666-671. e1. doi: 10.1016/j.jpeds.2014.11.059
52. Fjaertoft G, Hakansson L, Foucard T, et al. CD64 (Fcgamma receptor I) cell surface expression on maturing neutrophils from preterm and term newborn infants. Acta Paediatr. 2005;94(3):295-302. doi: 10.1111/j.1651-2227.2005.tb03072.x
53. Tian Z, Sutton BJ, Zhang X. Distribution of rat neonatal Fc receptor in the principal organs of neonatal and pubertal rats. J Recept Signal Transduct Res. 2014;34(2):137-142. doi: 10.3109/10799893.2013.865745
54. Cianga C, Cianga P, Plamadeala P, et al. Nonclassical major histocompatibility complex I-like Fc neonatal receptor (FcRn) expression in neonatal human tissues. Hum Immunol. 2011;72(12):1176-1187. doi: 10.1016/j.humimm.2011.08.020
55. Mankarious S, Lee M, Fischer S, et al. The half-lives of IgG subclasses and specific antibodies in patients with primary immunodeficiency who are receiving intravenously administered immunoglobulin. J Lab Clin Med. 1988;112(5):634-640.
56. Aksu G, Genel F, Koturoglu G, et al. Serum immunoglobulin (IgG, IgM, IgA) and IgG subclass concentrations in healthy children: a study using nephelometric technique. Turk J Pediatr. 2006;48(1):19-24.
57. He XS, Holmes TH, Zhang C, et al. Cellular immune responses in children and adults receiving inactivated or live attenuated influenza vaccines. J Virology. 2006;80:11756-11766. doi: 10.1128/JVI.01460-06
58. Xu Z, Davis HM, Zhou H. Rational development and utilization of antibody-based therapeutic proteins in pediatrics. Pharmacol Ther. 2013;137:225-247.
59. Purple Book. Database of Licensed Biological Products. 2021. Available online: https://purplebooksearch.fda.gov. Accessed on July 29, 2021.
60. Kozlov IG. Monoklonal'nye antitela — novaya era v farmakologii i terapii. Lechebnoe delo. 2006;(1):26-31. (In Russ).
61. FDA's Center for Drug Evaluation and Research (CDER). Novel Drug Approvals for 2016. Available online: https://www.fda.gov/drugs/new-drugs-fda-cders-new-molecular-entities-and-new-therapeutic-biological-products/novel-drug-approvals-2016. Accessed on July 29, 2021.
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For citations:
Kolbin A.S., Yemelyanova L.I. The Use of Biotechnological Drugs in Pediatrics on the Example of Monoclonal Antibodies: Clinical Pharmacology View. Pediatric pharmacology. 2021;18(4):304-313. (In Russ.) https://doi.org/10.15690/pf.v18i4.2293
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