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Pharmacokinetics and Pharmacodynamics Estimation of Eculizumab in a 2-Year-Old Girl With Atypical Hemolytic Uremic Syndrome: A Case Report With 4-Year Follow-Up

Background: Eculizumab has dramatically changed poor outcomes of complement-mediated atypical hemolytic uremic syndrome (aHUS) as first-line treatment. Discontinuation of eculizumab remains challenging, and doctor's visits every 2 weeks for intravenous injection because of standard dosing proto...

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Autores principales: Saida, Ken, Fukuda, Tsuyoshi, Mizuno, Kana, Ogura, Masao, Kamei, Koichi, Ito, Shuichi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6929516/
https://www.ncbi.nlm.nih.gov/pubmed/31921730
http://dx.doi.org/10.3389/fped.2019.00519
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author Saida, Ken
Fukuda, Tsuyoshi
Mizuno, Kana
Ogura, Masao
Kamei, Koichi
Ito, Shuichi
author_facet Saida, Ken
Fukuda, Tsuyoshi
Mizuno, Kana
Ogura, Masao
Kamei, Koichi
Ito, Shuichi
author_sort Saida, Ken
collection PubMed
description Background: Eculizumab has dramatically changed poor outcomes of complement-mediated atypical hemolytic uremic syndrome (aHUS) as first-line treatment. Discontinuation of eculizumab remains challenging, and doctor's visits every 2 weeks for intravenous injection because of standard dosing protocols is a huge burden. The Ultra-high cost of eculizumab is also an issue. We attempted to establish a personalized dosing regimen of eculizumab based on pharmacokinetics and pharmacodynamics in a 2-year-old girl with aHUS with a C3 mutation. Case presentation: She developed aHUS at 5 months of age and was successfully treated with eculizumab. At 2 years of age, we measured eculizumab concentrations and performed pharmacokinetics and pharmacodynamics analysis to optimize her dosing protocol. Her blood concentrations at every 2-, 3-, and 4-week intervals were simulated. Pharmacokinetics analysis showed that her eculizumab clearance was 40% lower than the population mean reported for aHUS. Pharmacokinetic simulation suggested that the 2- and 3-week interval regimen could be sufficient to achieve an efficient trough concentration (>100 μg/mL). We simulated her individual pharmacokinetics profile at 4 years of age with consideration of her growth, which still showed complete inhibition of the alternative complement pathway with the 3-week interval regimen. We continued the 300-mg eculizumab infusion every 3 weeks while CH50 levels were constantly maintained at undetectably low concentrations with no recurrence until 6 years of age. Conclusions: Pharmacokinetics and pharmacodynamics estimation was useful for establishing a personalized dosing regimen for eculizumab and reducing the patient's burden and high medical costs.
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spelling pubmed-69295162020-01-09 Pharmacokinetics and Pharmacodynamics Estimation of Eculizumab in a 2-Year-Old Girl With Atypical Hemolytic Uremic Syndrome: A Case Report With 4-Year Follow-Up Saida, Ken Fukuda, Tsuyoshi Mizuno, Kana Ogura, Masao Kamei, Koichi Ito, Shuichi Front Pediatr Pediatrics Background: Eculizumab has dramatically changed poor outcomes of complement-mediated atypical hemolytic uremic syndrome (aHUS) as first-line treatment. Discontinuation of eculizumab remains challenging, and doctor's visits every 2 weeks for intravenous injection because of standard dosing protocols is a huge burden. The Ultra-high cost of eculizumab is also an issue. We attempted to establish a personalized dosing regimen of eculizumab based on pharmacokinetics and pharmacodynamics in a 2-year-old girl with aHUS with a C3 mutation. Case presentation: She developed aHUS at 5 months of age and was successfully treated with eculizumab. At 2 years of age, we measured eculizumab concentrations and performed pharmacokinetics and pharmacodynamics analysis to optimize her dosing protocol. Her blood concentrations at every 2-, 3-, and 4-week intervals were simulated. Pharmacokinetics analysis showed that her eculizumab clearance was 40% lower than the population mean reported for aHUS. Pharmacokinetic simulation suggested that the 2- and 3-week interval regimen could be sufficient to achieve an efficient trough concentration (>100 μg/mL). We simulated her individual pharmacokinetics profile at 4 years of age with consideration of her growth, which still showed complete inhibition of the alternative complement pathway with the 3-week interval regimen. We continued the 300-mg eculizumab infusion every 3 weeks while CH50 levels were constantly maintained at undetectably low concentrations with no recurrence until 6 years of age. Conclusions: Pharmacokinetics and pharmacodynamics estimation was useful for establishing a personalized dosing regimen for eculizumab and reducing the patient's burden and high medical costs. Frontiers Media S.A. 2019-12-17 /pmc/articles/PMC6929516/ /pubmed/31921730 http://dx.doi.org/10.3389/fped.2019.00519 Text en Copyright © 2019 Saida, Fukuda, Mizuno, Ogura, Kamei and Ito. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Pediatrics
Saida, Ken
Fukuda, Tsuyoshi
Mizuno, Kana
Ogura, Masao
Kamei, Koichi
Ito, Shuichi
Pharmacokinetics and Pharmacodynamics Estimation of Eculizumab in a 2-Year-Old Girl With Atypical Hemolytic Uremic Syndrome: A Case Report With 4-Year Follow-Up
title Pharmacokinetics and Pharmacodynamics Estimation of Eculizumab in a 2-Year-Old Girl With Atypical Hemolytic Uremic Syndrome: A Case Report With 4-Year Follow-Up
title_full Pharmacokinetics and Pharmacodynamics Estimation of Eculizumab in a 2-Year-Old Girl With Atypical Hemolytic Uremic Syndrome: A Case Report With 4-Year Follow-Up
title_fullStr Pharmacokinetics and Pharmacodynamics Estimation of Eculizumab in a 2-Year-Old Girl With Atypical Hemolytic Uremic Syndrome: A Case Report With 4-Year Follow-Up
title_full_unstemmed Pharmacokinetics and Pharmacodynamics Estimation of Eculizumab in a 2-Year-Old Girl With Atypical Hemolytic Uremic Syndrome: A Case Report With 4-Year Follow-Up
title_short Pharmacokinetics and Pharmacodynamics Estimation of Eculizumab in a 2-Year-Old Girl With Atypical Hemolytic Uremic Syndrome: A Case Report With 4-Year Follow-Up
title_sort pharmacokinetics and pharmacodynamics estimation of eculizumab in a 2-year-old girl with atypical hemolytic uremic syndrome: a case report with 4-year follow-up
topic Pediatrics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6929516/
https://www.ncbi.nlm.nih.gov/pubmed/31921730
http://dx.doi.org/10.3389/fped.2019.00519
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