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27-09-2024 | Anakinra | Original Research Article

Physiologically Based Pharmacokinetic Modelling in Critically Ill Children Receiving Anakinra While on Extracorporeal Life Support

Authors: Samuel Dubinsky, Abdullah Hamadeh, Carina Imburgia, Autumn McKnite, J. Porter Hunt, Kristy Wong, Cassandra Rice, Joseph Rower, Kevin Watt, Andrea Edginton

Published in: Clinical Pharmacokinetics | Issue 9/2024

Abstract

Background and Objective

Because of the pathophysiological changes associated with critical illness and the use of extracorporeal life support (ECLS) such as continuous renal replacement therapy (CRRT) and extracorporeal membrane oxygenation (ECMO), the pharmacokinetics of drugs are often altered. The objective of this study was to develop a physiologically based pharmacokinetic (PBPK) model for anakinra in children that accounts for the physiological changes associated with critical illness and ECLS technology to guide appropriate pharmacotherapy.

Methods

A PBPK model for anakinra was first developed in healthy individuals prior to extrapolating to critically ill children receiving ECLS. To account for the impact of anakinra clearance by the dialysis circuit, a CRRT compartment was added to the pediatric PBPK model and parameterized using data from a previously published ex-vivo study. Additionally, an ECMO compartment was added to the whole-body structure to create the final anakinra ECLS-PBPK model. The final model structure was validated by comparing predicted concentrations with observed patient data. Due to limited information in guiding anakinra dosing in this population, in-silico dose simulations were conducted to provide baseline recommendations.

Results

By accounting for changes in physiology and the addition of ECLS compartments, the final ECLS-PBPK model predicted the observed plasma concentrations in an adolescent receiving subcutaneous anakinra. Furthermore, dosing simulations suggest that anakinra exposure in adolescents receiving ECLS is similar to that in healthy counterparts.

Conclusion

The anakinra ECLS-PBPK model developed in this study is the first to predict plasma concentrations in a population receiving simultaneous CRRT and ECMO. Dosing simulations provided may be used to inform anakinra use in critically ill children and guide future clinical trial planning.

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Singer M, Deutschman CS, Seymour CW, et al. The third international consensus definitions for sepsis and septic shock (sepsis-3). JAMA. 2016;315(8):801–10. https://doi.org/10.1001/jama.2016.0287.CrossRefPubMedPubMedCentral

Fleischmann-Struzek C, Goldfarb DM, Schlattmann P, Schlapbach LJ, Reinhart K, Kissoon N. The global burden of paediatric and neonatal sepsis: a systematic review. Lancet Respir Med. 2018;6(3):223–30. https://doi.org/10.1016/S2213-2600(18)30063-8.CrossRefPubMed

Balamuth F, Weiss SL, Neuman MI, et al. Pediatric severe sepsis in US children’s hospitals. Pediatr Crit Care Med J Soc Crit Care Med World Fed Pediatr Intensive Crit Care Soc. 2014;15(9):798–805. https://doi.org/10.1097/PCC.0000000000000225.CrossRef

Odetola FO, Gebremariam A, Freed GL. Patient and hospital correlates of clinical outcomes and resource utilization in severe pediatric sepsis. Pediatrics. 2007;119(3):487–94. https://doi.org/10.1542/peds.2006-2353.CrossRefPubMed

Ruth A, McCracken CE, Fortenberry JD, Hall M, Simon HK, Hebbar KB. Pediatric severe sepsis: current trends and outcomes from the pediatric health information systems database. Pediatr Crit Care Med J Soc Crit Care Med World Fed Pediatr Intensive Crit Care Soc. 2014;15(9):828–38. https://doi.org/10.1097/PCC.0000000000000254.CrossRef

Watson RS, Crow SS, Hartman ME, Lacroix J, Odetola FO. Epidemiology and outcomes of pediatric multiple organ dysfunction syndrome. Pediatr Crit Care Med J Soc Crit Care Med World Fed Pediatr Intensive Crit Care Soc. 2017;18(3):S4–16. https://doi.org/10.1097/PCC.0000000000001047.CrossRef

Weiss SL, Peters MJ, Alhazzani W, et al. Surviving sepsis campaign international guidelines for the management of septic shock and sepsis-associated organ dysfunction in children. Pediatr Crit Care Med J Soc Crit Care Med World Fed Pediatr Intensive Crit Care Soc. 2020;21(2):e52–106. https://doi.org/10.1097/PCC.0000000000002198.CrossRef

Leteurtre S, Martinot A, Duhamel A, et al. Validation of the paediatric logistic organ dysfunction (PELOD) score: prospective, observational, multicentre study. Lancet Lond Engl. 2003;362(9379):192–7. https://doi.org/10.1016/S0140-6736(03)13908-6.CrossRef

Shakoory B, Carcillo JA, Chatham WW, et al. Interleukin-1 receptor blockade is associated with reduced mortality in sepsis patients with features of macrophage activation syndrome: reanalysis of a prior phase III trial. Crit Care Med. 2016;44(2):275–81. https://doi.org/10.1097/CCM.0000000000001402.CrossRefPubMedPubMedCentral

10.

Carcillo JA, Halstead ES, Hall MW, et al. Three hypothetical inflammation pathobiology phenotypes and pediatric sepsis-induced multiple organ failure outcome. Pediatr Crit Care Med J Soc Crit Care Med World Fed Pediatr Intensive Crit Care Soc. 2017;18(6):513–23. https://doi.org/10.1097/PCC.0000000000001122.CrossRef

11.

Seymour CW, Kennedy JN, Wang S, et al. Derivation, validation, and potential treatment implications of novel clinical phenotypes for sepsis. JAMA. 2019;321(20):2003–17. https://doi.org/10.1001/jama.2019.5791.CrossRefPubMedPubMedCentral

12.

Leventogiannis K, Kyriazopoulou E, Antonakos N, et al. Toward personalized immunotherapy in sepsis: the PROVIDE randomized clinical trial. Cell Rep Med. 2022;3(11): 100817. https://doi.org/10.1016/j.xcrm.2022.100817.CrossRefPubMedPubMedCentral

13.

Dean JM. Evolution of the collaborative pediatric critical care research network (CPCCRN). Pediatr Crit Care Med J Soc Crit Care Med World Fed Pediatr Intensive Crit Care Soc. 2022;23(12):1049–55. https://doi.org/10.1097/PCC.0000000000003098.CrossRef

14.

Tandukar S, Palevsky PM. Continuous renal replacement therapy: who, when, why, and how. Chest. 2019;155(3):626–38. https://doi.org/10.1016/j.chest.2018.09.004.CrossRefPubMed

15.

Ricci Z, Goldstein SL. Pediatric continuous renal replacement therapy. Contrib Nephrol. 2016;187:121–30. https://doi.org/10.1159/000442370.CrossRefPubMed

16.

Cohen S, Hurd E, Cush J, et al. Treatment of rheumatoid arthritis with anakinra, a recombinant human interleukin-1 receptor antagonist, in combination with methotrexate: results of a twenty-four-week, multicenter, randomized, double-blind, placebo-controlled trial. Arthritis Rheum. 2002;46(3):614–24. https://doi.org/10.1002/art.10141.CrossRefPubMed

17.

Goldbach-Mansky R, Dailey NJ, Canna SW, et al. Neonatal-onset multisystem inflammatory disease responsive to interleukin-1beta inhibition. N Engl J Med. 2006;355(6):581–92. https://doi.org/10.1056/NEJMoa055137.CrossRefPubMedPubMedCentral

18.

Carter SJ, Tattersall RS, Ramanan AV. Macrophage activation syndrome in adults: recent advances in pathophysiology, diagnosis and treatment. Rheumatol Oxf Engl. 2019;58(1):5–17. https://doi.org/10.1093/rheumatology/key006.CrossRef

19.

Kumar B, Aleem S, Saleh H, Petts J, Ballas ZK. A personalized diagnostic and treatment approach for macrophage activation syndrome and secondary hemophagocytic lymphohistiocytosis in adults. J Clin Immunol. 2017;37(7):638–43. https://doi.org/10.1007/s10875-017-0439-x.CrossRefPubMed

20.

Rajasekaran S, Kruse K, Kovey K, et al. Therapeutic role of anakinra, an interleukin-1 receptor antagonist, in the management of secondary hemophagocytic lymphohistiocytosis/sepsis/multiple organ dysfunction/macrophage activating syndrome in critically ill children*. Pediatr Crit Care Med J Soc Crit Care Med World Fed Pediatr Intensive Crit Care Soc. 2014;15(5):401–8. https://doi.org/10.1097/PCC.0000000000000078.CrossRef

21.

Fisher CJ, Slotman GJ, Opal SM, et al. Initial evaluation of human recombinant interleukin-1 receptor antagonist in the treatment of sepsis syndrome: a randomized, open-label, placebo-controlled multicenter trial. Crit Care Med. 1994;22(1):12–21. https://doi.org/10.1097/00003246-199401000-00008.CrossRefPubMed

22.

Fisher CJ, Dhainaut JF, Opal SM, et al. Recombinant human interleukin 1 receptor antagonist in the treatment of patients with sepsis syndrome. Results from a randomized, double-blind, placebo-controlled trial. Phase III rhIL-1ra sepsis syndrome study group. JAMA. 1994;271(23):1836–43.CrossRefPubMed

23.

Opal SM, Fisher CJ, Dhainaut JF, et al. Confirmatory interleukin-1 receptor antagonist trial in severe sepsis: a phase III, randomized, double-blind, placebo-controlled, multicenter trial. The interleukin-1 receptor antagonist sepsis investigator group. Crit Care Med. 1997;25(7):1115–24. https://doi.org/10.1097/00003246-199707000-00010.CrossRefPubMed

24.

Watt KM, Cohen-Wolkowiez M, Barrett JS, et al. Physiologically based pharmacokinetic approach to determine dosing on extracorporeal life support: fluconazole in children on ECMO. CPT Pharmacomet Syst Pharmacol. 2018;7(10):629–37. https://doi.org/10.1002/psp4.12338.CrossRef

25.

Fuhr LM, Hanke N, Meibohm B, Lehr T. Effective removal of dabigatran by idarucizumab or hemodialysis: a physiologically based pharmacokinetic modeling analysis. Clin Pharmacokinet. 2020;59(6):809–25. https://doi.org/10.1007/s40262-019-00857-y.CrossRefPubMedPubMedCentral

26.

Dubinsky SDJ, Watt KM, Imburgia CE, et al. Anakinra removal by continuous renal replacement therapy: an ex vivo analysis. Crit Care Explor. 2023;5(12): e1010. https://doi.org/10.1097/CCE.0000000000001010.CrossRefPubMedPubMedCentral

27.

Niederalt C, Kuepfer L, Solodenko J, et al. A generic whole body physiologically based pharmacokinetic model for therapeutic proteins in PK-Sim. J Pharmacokinet Pharmacodyn. 2018;45(2):235–57. https://doi.org/10.1007/s10928-017-9559-4.CrossRefPubMed

28.

Willmann S, Höhn K, Edginton A, et al. Development of a physiology-based whole-body population model for assessing the influence of individual variability on the pharmacokinetics of drugs. J Pharmacokinet Pharmacodyn. 2007;34(3):401–31. https://doi.org/10.1007/s10928-007-9053-5.CrossRefPubMed

29.

Schlender JF, Meyer M, Thelen K, et al. Development of a whole-body physiologically based pharmacokinetic approach to assess the pharmacokinetics of drugs in elderly individuals. Clin Pharmacokinet. 2016;55(12):1573–89. https://doi.org/10.1007/s40262-016-0422-3.CrossRefPubMedPubMedCentral

30.

Edginton AN, Schmitt W, Willmann S. Development and evaluation of a generic physiologically based pharmacokinetic model for children. Clin Pharmacokinet. 2006;45(10):1013–34. https://doi.org/10.2165/00003088-200645100-00005.CrossRefPubMed

31.

Gill KL, Gardner I, Li L, Jamei M. A bottom-up whole-body physiologically based pharmacokinetic model to mechanistically predict tissue distribution and the rate of subcutaneous absorption of therapeutic proteins. AAPS J. 2016;18(1):156–70. https://doi.org/10.1208/s12248-015-9819-4.CrossRefPubMed

32.

Liebner R, Mathaes R, Meyer M, Hey T, Winter G, Besheer A. Protein HESylation for half-life extension: synthesis, characterization and pharmacokinetics of HESylated anakinra. Eur J Pharm Biopharm Off J Arbeitsgemeinschaft Pharm Verfahrenstechnik EV. 2014;87(2):378–85. https://doi.org/10.1016/j.ejpb.2014.03.010.CrossRef

33.

Pan X, Stader F, Abduljalil K, et al. Development and application of a physiologically-based pharmacokinetic model to predict the pharmacokinetics of therapeutic proteins from full-term neonates to adolescents. AAPS J. 2020;22(4):76. https://doi.org/10.1208/s12248-020-00460-1.CrossRefPubMed

34.

Schaller S, Willmann S, Lippert J, et al. A generic integrated physiologically based whole-body model of the glucose-insulin-glucagon regulatory system. CPT Pharmacomet Syst Pharmacol. 2013;2(8): e65. https://doi.org/10.1038/psp.2013.40.CrossRef

35.

Glassman PM, Balthasar JP. Physiologically-based modeling of monoclonal antibody pharmacokinetics in drug discovery and development. Drug Metab Pharmacokinet. 2019;34(1):3–13. https://doi.org/10.1016/j.dmpk.2018.11.002.CrossRefPubMed

36.

Yang BB, Baughman S, Sullivan JT. Pharmacokinetics of anakinra in subjects with different levels of renal function. Clin Pharmacol Ther. 2003;74(1):85–94. https://doi.org/10.1016/S0009-9236(03)00094-8.CrossRefPubMed

37.

Malik PRV, Yeung CHT, Ismaeil S, Advani U, Djie S, Edginton AN. A physiological approach to pharmacokinetics in chronic kidney disease. J Clin Pharmacol. 2020;60(Suppl 1):S52–62. https://doi.org/10.1002/jcph.1713.CrossRefPubMed

38.

Malinoski D, Jafari F, Ewing T, et al. Standard prophylactic enoxaparin dosing leads to inadequate anti-Xa levels and increased deep venous thrombosis rates in critically ill trauma and surgical patients. J Trauma. 2010;68(4):874–80. https://doi.org/10.1097/TA.0b013e3181d32271.CrossRefPubMed

39.

Priglinger U, Delle Karth G, Geppert A, et al. Prophylactic anticoagulation with enoxaparin: Is the subcutaneous route appropriate in the critically ill? Crit Care Med. 2003;31(5):1405–9. https://doi.org/10.1097/01.CCM.0000059725.60509.A0.CrossRefPubMed

40.

Dörffler-Melly J, de Jonge E, Pont AC, et al. Bioavailability of subcutaneous low-molecular-weight heparin to patients on vasopressors. Lancet Lond Engl. 2002;359(9309):849–50. https://doi.org/10.1016/s0140-6736(02)07920-5.CrossRef

41.

Macdougall IC, Robson R, Opatrna S, et al. Pharmacokinetics and pharmacodynamics of intravenous and subcutaneous continuous erythropoietin receptor activator (CERA) in patients with chronic kidney disease. Clin J Am Soc Nephrol CJASN. 2006;1(6):1211–5. https://doi.org/10.2215/CJN.00730306.CrossRefPubMed

42.

Kaufman JS, Reda DJ, Fye CL, et al. Subcutaneous compared with intravenous epoetin in patients receiving hemodialysis. Department of Veterans Affairs Cooperative Study Group on Erythropoietin in Hemodialysis Patients. N Engl J Med. 1998;339(9):578–83. https://doi.org/10.1056/NEJM199808273390902.CrossRefPubMed

43.

Malik PRV, Edginton AN. Integration of ontogeny into a physiologically based pharmacokinetic model for monoclonal antibodies in premature infants. J Clin Pharmacol. 2020;60(4):466–76. https://doi.org/10.1002/jcph.1540.CrossRefPubMed

44.

Green EA, Metz D, Galinsky R, et al. Anakinra pilot—a clinical trial to demonstrate safety, feasibility and pharmacokinetics of interleukin 1 receptor antagonist in preterm infants. Front Immunol. 2022;13:1022104. https://doi.org/10.3389/fimmu.2022.1022104.CrossRefPubMedPubMedCentral

45.

Cayabyab RG, Jones CA, Kwong KYC, et al. Interleukin-1beta in the bronchoalveolar lavage fluid of premature neonates: a marker for maternal chorioamnionitis and predictor of adverse neonatal outcome. J Matern-Fetal Neonatal Med. 2003;14(3):205–11. https://doi.org/10.1080/jmf.14.3.205.211.CrossRefPubMed

46.

Urien S, Bardin C, Bader-Meunier B, et al. Anakinra pharmacokinetics in children and adolescents with systemic-onset juvenile idiopathic arthritis and autoinflammatory syndromes. BMC Pharmacol Toxicol. 2013;14:40. https://doi.org/10.1186/2050-6511-14-40.CrossRefPubMedPubMedCentral

47.

Ilowite N, Porras O, Reiff A, et al. Anakinra in the treatment of polyarticular-course juvenile rheumatoid arthritis: safety and preliminary efficacy results of a randomized multicenter study. Clin Rheumatol. 2009;28(2):129–37. https://doi.org/10.1007/s10067-008-0995-9.CrossRefPubMed

48.

Anderson HL, Coran AG, Drongowski RA, Ha HJ, Bartlett RH. Extracellular fluid and total body water changes in neonates undergoing extracorporeal membrane oxygenation. J Pediatr Surg. 1992;27(8):1003–7. https://doi.org/10.1016/0022-3468(92)90547-k.CrossRefPubMed

49.

Vrancken SL, Heijst AF, Zegers M, et al. Influence of volume replacement with colloids versus crystalloids in neonates on venoarterial extracorporeal membrane oxygenation on fluid retention, fluid balance, and ECMO runtime. ASAIO J Am Soc Artif Intern Organs. 2005;51(6):808–12. https://doi.org/10.1097/01.mat.0000183474.01675.3a.CrossRef

50.

Selewski DT, Askenazi DJ, Bridges BC, et al. The impact of fluid overload on outcomes in children treated with extracorporeal membrane oxygenation: a multi-centre retrospective cohort study. Pediatr Crit Care Med J Soc Crit Care Med World Fed Pediatr Intensive Crit Care Soc. 2017;18(12):1126–35. https://doi.org/10.1097/PCC.0000000000001349.CrossRef

51.

Radke C, Horn D, Lanckohr C, et al. Development of a physiologically based pharmacokinetic modelling approach to predict the pharmacokinetics of vancomycin in critically ill septic patients. Clin Pharmacokinet. 2017;56(7):759–79. https://doi.org/10.1007/s40262-016-0475-3.CrossRefPubMed

52.

Mehta P, Cron RQ, Hartwell J, Manson JJ, Tattersall RS. Silencing the cytokine storm: the use of intravenous anakinra in haemophagocytic lymphohistiocytosis or macrophage activation syndrome. Lancet Rheumatol. 2020;2(6):e358–67. https://doi.org/10.1016/S2665-9913(20)30096-5.CrossRefPubMedPubMedCentral

53.

Cavalli G, De Luca G, Campochiaro C, et al. Interleukin-1 blockade with high-dose anakinra in patients with COVID-19, acute respiratory distress syndrome, and hyperinflammation: a retrospective cohort study. Lancet Rheumatol. 2020;2(6):e325–31. https://doi.org/10.1016/S2665-9913(20)30127-2.CrossRefPubMedPubMedCentral

54.

Yang J, Jain S, Capparelli EV, et al. Anakinra treatment in patients with acute kawasaki disease with coronary artery aneurysms: a phase i/iia trial. J Pediatr. 2022;243:173-180.e8. https://doi.org/10.1016/j.jpeds.2021.12.035.CrossRefPubMed

55.

Bami S, Vagrecha A, Soberman D, et al. The use of anakinra in the treatment of secondary hemophagocytic lymphohistiocytosis. Pediatr Blood Cancer. 2020;67(11): e28581. https://doi.org/10.1002/pbc.28581.CrossRefPubMed

56.

Phadke O, Rouster-Stevens K, Giannopoulos H, Chandrakasan S, Prahalad S. Intravenous administration of anakinra in children with macrophage activation syndrome. Pediatr Rheumatol Online J. 2021;19(1):98. https://doi.org/10.1186/s12969-021-00585-3.CrossRefPubMedPubMedCentral

57.

Kineret (anakinra). Prescribing Information. Stockholm, Sweden. Swedish Orphan Biovitrum AB INC. March 2018.

58.

Yang BB, Gozzi P, Sullivan JT. Pharmacokinetics of anakinra in subjects of heavier vs lighter body weights. Clin Transl Sci. 2019;12(4):371–8. https://doi.org/10.1111/cts.12622.CrossRefPubMedPubMedCentral

59.

Granowitz EV, Porat R, Mier JW, et al. Pharmacokinetics, safety and immunomodulatory effects of human recombinant interleukin-1 receptor antagonist in healthy humans. Cytokine. 1992;4(5):353–60. https://doi.org/10.1016/1043-4666(92)90078-6.CrossRefPubMed

60.

Dubinsky S, Watt K, Saleeb S, et al. Pharmacokinetics of commonly used medications in children receiving continuous renal replacement therapy: a systematic review of current literature. Clin Pharmacokinet. 2022;61(2):189–229. https://doi.org/10.1007/s40262-021-01085-z.CrossRefPubMed

61.

Sutiman N, Koh JC, Watt K, et al. Pharmacokinetics alterations in critically ill pediatric patients on extracorporeal membrane oxygenation: a systematic review. Front Pediatr. 2020;8:260. https://doi.org/10.3389/fped.2020.00260.CrossRefPubMedPubMedCentral

62.

Choi G, Gomersall CD, Tian Q, Joynt GM, Freebairn R, Lipman J. Principles of antibacterial dosing in continuous renal replacement therapy. Crit Care Med. 2009;37(7):2268–82. https://doi.org/10.1097/CCM.0b013e3181aab3d0.CrossRefPubMed

63.

Bugge JF. Influence of renal replacement therapy on pharmacokinetics in critically ill patients. Best Pract Res Clin Anaesthesiol. 2004;18(1):175–87. https://doi.org/10.1016/j.bpa.2003.09.002.CrossRefPubMed

64.

Pistolesi V, Morabito S, Di Mario F, Regolisti G, Cantarelli C, Fiaccadori E. A guide to understanding antimicrobial drug dosing in critically ill patients on renal replacement therapy. Antimicrob Agents Chemother. 2019;63(8):e00583-e619. https://doi.org/10.1128/AAC.00583-19.CrossRefPubMedPubMedCentral

65.

Hoff BM, Maker JH, Dager WE, Heintz BH. Antibiotic dosing for critically ill adult patients receiving intermittent hemodialysis, prolonged intermittent renal replacement therapy, and continuous renal replacement therapy: an update. Ann Pharmacother. 2020;54(1):43–55. https://doi.org/10.1177/1060028019865873.CrossRefPubMed

66.

Li AMMY, Gomersall CD, Choi G, Tian Q, Joynt GM, Lipman J. A systematic review of antibiotic dosing regimens for septic patients receiving continuous renal replacement therapy: do current studies supply sufficient data? J Antimicrob Chemother. 2009;64(5):929–37. https://doi.org/10.1093/jac/dkp302.CrossRefPubMed

67.

Antonucci E, Lamanna I, Fagnoul D, Vincent JL, De Backer D, Silvio TF. The impact of renal failure and renal replacement therapy on outcome during extracorporeal membrane oxygenation therapy. Artif Organs. 2016;40(8):746–54. https://doi.org/10.1111/aor.12695.CrossRefPubMed

68.

Fleming GM, Sahay R, Zappitelli M, et al. The incidence of acute kidney injury and its effect on neonatal and pediatric ECMO outcomes: a multicenter report from the KIDMO study group. Pediatr Crit Care Med J Soc Crit Care Med World Fed Pediatr Intensive Crit Care Soc. 2016;17(12):1157–69. https://doi.org/10.1097/PCC.0000000000000970.CrossRef

69.

Haneya A, Diez C, Philipp A, et al. Impact of acute kidney injury on outcome in patients with severe acute respiratory failure receiving extracorporeal membrane oxygenation. Crit Care Med. 2015;43(9):1898–906. https://doi.org/10.1097/CCM.0000000000001141.CrossRefPubMed

70.

Gorga SM, Lima L, Askenazi DJ, et al. Fluid balance management informs renal replacement therapy use during pediatric extracorporeal membrane oxygenation: a survey report from the kidney intervention during extracorporeal membrane oxygenation group. ASAIO J Am Soc Artif Intern Organs. 2022;68(3):407–12. https://doi.org/10.1097/MAT.0000000000001471.CrossRef

71.

Maniscalco V, Abu-Rumeileh S, Mastrolia MV, et al. The off-label use of anakinra in pediatric systemic autoinflammatory diseases. Ther Adv Musculoskelet Dis. 2020;12:17597. https://doi.org/10.1177/1759720X20959575.CrossRef

72.

Schwartz SP, Walker TC, Kihlstrom M, et al. Extracorporeal membrane oxygenation for COVID-19-associated multisystem inflammatory syndrome in a 5-year-old. Am Surg. 2022;88(2):174–6. https://doi.org/10.1177/0003134820983198.CrossRefPubMedPubMedCentral

73.

Maunier L, Charbel R, Lambert V, Tissières P, The CLOVIS Study Group. Anakinra in pediatric acute fulminant myocarditis. Ann Intensive Care. 2022;12:85. https://doi.org/10.1186/s13613-022-01054-0.CrossRef

74.

Çaǧlayan Ş, Sönmez HE, Otar Yener G, et al. Anakinra treatment in multisystemic inflammatory syndrome in children (MIS-C) associated with COVID-19. Front Pediatr. 2022;10: 942455. https://doi.org/10.3389/fped.2022.942455.CrossRefPubMedPubMedCentral

75.

Cloyd C, Sargel C. 1014: Anakinra dosing for macrophage activation syndrome during continuous renal replacement therapy. Crit Care Med. 2022;50(1):504. https://doi.org/10.1097/01.ccm.0000810380.26200.b7.CrossRef

76.

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. https://doi.org/10.1007/s40262-014-0208-4.CrossRefPubMed

77.

Malik P, Edginton A. Pediatric physiology in relation to the pharmacokinetics of monoclonal antibodies. Expert Opin Drug Metab Toxicol. 2018;14(6):585–99. https://doi.org/10.1080/17425255.2018.1482278.CrossRefPubMed

78.

Zhang Y, Wei X, Bajaj G, et al. Challenges and considerations for development of therapeutic proteins in pediatric patients. J Clin Pharmacol. 2015;55(Suppl 3):S103-115. https://doi.org/10.1002/jcph.382.CrossRefPubMed

79.

Quartier P, Allantaz F, Cimaz R, et al. A multicentre, randomised, double-blind, placebo-controlled trial with the interleukin-1 receptor antagonist anakinra in patients with systemic-onset juvenile idiopathic arthritis (ANAJIS trial). Ann Rheum Dis. 2011;70(5):747–54. https://doi.org/10.1136/ard.2010.134254.CrossRefPubMed

80.

Morales Castro D, Dresser L, Granton J, Fan E. Pharmacokinetic alterations associated with critical illness. Clin Pharmacokinet. 2023;62(2):209–20. https://doi.org/10.1007/s40262-023-01213-x.CrossRefPubMedPubMedCentral

81.

Cihlar R, Sramek V, Papiez A, Penka M, Suk P. Pharmacokinetic comparison of subcutaneous and intravenous nadroparin administration for thromboprophylaxis in critically ill patients on vasopressors. Pharmacology. 2020;105(1–2):73–8. https://doi.org/10.1159/000502847.CrossRefPubMed

82.

Ferenbach DA, Bonventre JV. Acute kidney injury and chronic kidney disease: from the laboratory to the clinic. Nephrol Ther. 2016;12(Suppl 1):S41–8. https://doi.org/10.1016/j.nephro.2016.02.005.CrossRefPubMedPubMedCentral

83.

Sato Y, Takahashi M, Yanagita M. Pathophysiology of AKI to CKD progression. Semin Nephrol. 2020;40(2):206–15. https://doi.org/10.1016/j.semnephrol.2020.01.011.CrossRefPubMed

84.

Lim K, McGregor G, Coggan AR, Lewis GD, Moe SM. Cardiovascular functional changes in chronic kidney disease: integrative physiology, pathophysiology and applications of cardiopulmonary exercise testing. Front Physiol. 2020;11: 572355. https://doi.org/10.3389/fphys.2020.572355.CrossRefPubMedPubMedCentral

85.

Katulka EK, Hirt AE, Kirkman DL, Edwards DG, Witman MAH. Altered vascular function in chronic kidney disease: evidence from passive leg movement. Physiol Rep. 2019;7(8): e14075. https://doi.org/10.14814/phy2.14075.CrossRefPubMedPubMedCentral

86.

Ngo B, Rongey C, Hiscox B, Rendell M, Woodley D, Smogorzewski M. Skin blood flow in patients with stage 5 chronic kidney disease on hemodialysis. J Ren Nutr Off J Counc Ren Nutr Natl Kidney Found. 2010;20(5 Suppl):S89-94. https://doi.org/10.1053/j.jrn.2010.06.008.CrossRef

Title: Physiologically Based Pharmacokinetic Modelling in Critically Ill Children Receiving Anakinra While on Extracorporeal Life Support
Authors: Samuel Dubinsky
Abdullah Hamadeh
Carina Imburgia
Autumn McKnite
J. Porter Hunt
Kristy Wong
Cassandra Rice
Joseph Rower
Kevin Watt
Andrea Edginton
Publication date: 27-09-2024
Publisher: Springer International Publishing
Keywords: Anakinra
ECMO
ECMO
Pharmacokinetics
Published in: Clinical Pharmacokinetics / Issue 9/2024
Print ISSN: 0312-5963
Electronic ISSN: 1179-1926
DOI: https://doi.org/10.1007/s40262-024-01424-w

Keynote webinar | Spotlight on modern management of frailty

Springer Medicine

Physiologically Based Pharmacokinetic Modelling in Critically Ill Children Receiving Anakinra While on Extracorporeal Life Support

Abstract

Background and Objective

Methods

Results

Conclusion

Keynote webinar | Spotlight on modern management of frailty

Springer Medicine

Abstract

Background and Objective

Methods

Results

Conclusion

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