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Population Pharmacokinetic/Pharmacodynamic Modeling of Methylprednisolone in Neonates Undergoing Cardiopulmonary Bypass
Methylprednisolone is used in neonates to modulate cardiopulmonary bypass (CPB)–induced inflammation, but optimal dosing and exposure are unknown. We used plasma methylprednisolone and interleukin (IL)‐6 and IL‐10 concentrations from neonates enrolled in a randomized trial comparing one vs. two dose...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6930860/ https://www.ncbi.nlm.nih.gov/pubmed/31646767 http://dx.doi.org/10.1002/psp4.12470 |
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author | Hornik, Christoph P. Gonzalez, Daniel Dumond, Julie Wu, Huali Graham, Eric M. Hill, Kevin D. Cohen‐Wolkowiez, Michael |
author_facet | Hornik, Christoph P. Gonzalez, Daniel Dumond, Julie Wu, Huali Graham, Eric M. Hill, Kevin D. Cohen‐Wolkowiez, Michael |
author_sort | Hornik, Christoph P. |
collection | PubMed |
description | Methylprednisolone is used in neonates to modulate cardiopulmonary bypass (CPB)–induced inflammation, but optimal dosing and exposure are unknown. We used plasma methylprednisolone and interleukin (IL)‐6 and IL‐10 concentrations from neonates enrolled in a randomized trial comparing one vs. two doses of methylprednisolone to develop indirect response population pharmacokinetic/pharmacodynamic models characterizing the exposure–response relationships. We applied the models to simulate methylprednisolone dosages resulting in the desired IL‐6 and ‐10 exposures, known mediators of CPB‐induced inflammation. A total of 64 neonates (median weight 3.2 kg, range 2.2–4.3) contributed 290 plasma methylprednisolone concentrations (range 1.07–12,700 ng/mL) and IL‐6 (0–681 pg/mL) and IL‐10 (0.1–1125 pg/mL). Methylprednisolone plasma exposure following a single 10 mg/kg intravenous dose inhibited IL‐6 and stimulated IL‐10 production when compared with placebo. Higher (30 mg/kg) or more frequent (twice) dosing did not confer additional benefit. Clinical efficacy studies are needed to evaluate the effect of optimized dosing on outcomes. |
format | Online Article Text |
id | pubmed-6930860 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-69308602019-12-27 Population Pharmacokinetic/Pharmacodynamic Modeling of Methylprednisolone in Neonates Undergoing Cardiopulmonary Bypass Hornik, Christoph P. Gonzalez, Daniel Dumond, Julie Wu, Huali Graham, Eric M. Hill, Kevin D. Cohen‐Wolkowiez, Michael CPT Pharmacometrics Syst Pharmacol Research Methylprednisolone is used in neonates to modulate cardiopulmonary bypass (CPB)–induced inflammation, but optimal dosing and exposure are unknown. We used plasma methylprednisolone and interleukin (IL)‐6 and IL‐10 concentrations from neonates enrolled in a randomized trial comparing one vs. two doses of methylprednisolone to develop indirect response population pharmacokinetic/pharmacodynamic models characterizing the exposure–response relationships. We applied the models to simulate methylprednisolone dosages resulting in the desired IL‐6 and ‐10 exposures, known mediators of CPB‐induced inflammation. A total of 64 neonates (median weight 3.2 kg, range 2.2–4.3) contributed 290 plasma methylprednisolone concentrations (range 1.07–12,700 ng/mL) and IL‐6 (0–681 pg/mL) and IL‐10 (0.1–1125 pg/mL). Methylprednisolone plasma exposure following a single 10 mg/kg intravenous dose inhibited IL‐6 and stimulated IL‐10 production when compared with placebo. Higher (30 mg/kg) or more frequent (twice) dosing did not confer additional benefit. Clinical efficacy studies are needed to evaluate the effect of optimized dosing on outcomes. John Wiley and Sons Inc. 2019-10-23 2019-12 /pmc/articles/PMC6930860/ /pubmed/31646767 http://dx.doi.org/10.1002/psp4.12470 Text en © 2019 The Authors. CPT: Pharmacometrics & Systems Pharmacology published by Wiley Periodicals, Inc. on behalf of the American Society for Clinical Pharmacology and Therapeutics. This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes. |
spellingShingle | Research Hornik, Christoph P. Gonzalez, Daniel Dumond, Julie Wu, Huali Graham, Eric M. Hill, Kevin D. Cohen‐Wolkowiez, Michael Population Pharmacokinetic/Pharmacodynamic Modeling of Methylprednisolone in Neonates Undergoing Cardiopulmonary Bypass |
title | Population Pharmacokinetic/Pharmacodynamic Modeling of Methylprednisolone in Neonates Undergoing Cardiopulmonary Bypass |
title_full | Population Pharmacokinetic/Pharmacodynamic Modeling of Methylprednisolone in Neonates Undergoing Cardiopulmonary Bypass |
title_fullStr | Population Pharmacokinetic/Pharmacodynamic Modeling of Methylprednisolone in Neonates Undergoing Cardiopulmonary Bypass |
title_full_unstemmed | Population Pharmacokinetic/Pharmacodynamic Modeling of Methylprednisolone in Neonates Undergoing Cardiopulmonary Bypass |
title_short | Population Pharmacokinetic/Pharmacodynamic Modeling of Methylprednisolone in Neonates Undergoing Cardiopulmonary Bypass |
title_sort | population pharmacokinetic/pharmacodynamic modeling of methylprednisolone in neonates undergoing cardiopulmonary bypass |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6930860/ https://www.ncbi.nlm.nih.gov/pubmed/31646767 http://dx.doi.org/10.1002/psp4.12470 |
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