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Maternal–Neonatal Raltegravir Population Pharmacokinetics Modeling: Implications for Initial Neonatal Dosing

Raltegravir readily crosses the placenta to the fetus with maternal use during pregnancy. After birth, neonatal raltegravir elimination is highly variable and often extremely prolonged, with some neonates demonstrating rising profiles after birth despite removal from the source of extrinsic raltegra...

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Autores principales: Lommerse, Jos, Clarke, Diana, Kerbusch, Thomas, Merdjan, Henri, Witjes, Han, Teppler, Hedy, Mirochnick, Mark, Acosta, Edward P., Wenning, Larissa, Nachman, Sharon, Chain, Anne
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6765695/
https://www.ncbi.nlm.nih.gov/pubmed/31215170
http://dx.doi.org/10.1002/psp4.12443
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author Lommerse, Jos
Clarke, Diana
Kerbusch, Thomas
Merdjan, Henri
Witjes, Han
Teppler, Hedy
Mirochnick, Mark
Acosta, Edward P.
Wenning, Larissa
Nachman, Sharon
Chain, Anne
author_facet Lommerse, Jos
Clarke, Diana
Kerbusch, Thomas
Merdjan, Henri
Witjes, Han
Teppler, Hedy
Mirochnick, Mark
Acosta, Edward P.
Wenning, Larissa
Nachman, Sharon
Chain, Anne
author_sort Lommerse, Jos
collection PubMed
description Raltegravir readily crosses the placenta to the fetus with maternal use during pregnancy. After birth, neonatal raltegravir elimination is highly variable and often extremely prolonged, with some neonates demonstrating rising profiles after birth despite removal from the source of extrinsic raltegravir. To establish an appropriate dosing regimen, an integrated maternal–neonatal pharmacokinetics model was built to predict raltegravir plasma concentrations in neonates with in utero raltegravir exposure. Postnatal age and body weight were used as structural covariates. The model predicted rising or decreasing neonatal elimination profiles based on the time of maternal drug administration relative to time of birth and degree of in utero drug disposition into the central and peripheral compartments. Based on this model, it is recommended to delay the first oral dose of raltegravir until 1–2 days of age in those neonates born to mothers who received raltegravir during pregnancy, labor, and delivery.
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spelling pubmed-67656952019-09-30 Maternal–Neonatal Raltegravir Population Pharmacokinetics Modeling: Implications for Initial Neonatal Dosing Lommerse, Jos Clarke, Diana Kerbusch, Thomas Merdjan, Henri Witjes, Han Teppler, Hedy Mirochnick, Mark Acosta, Edward P. Wenning, Larissa Nachman, Sharon Chain, Anne CPT Pharmacometrics Syst Pharmacol Research Raltegravir readily crosses the placenta to the fetus with maternal use during pregnancy. After birth, neonatal raltegravir elimination is highly variable and often extremely prolonged, with some neonates demonstrating rising profiles after birth despite removal from the source of extrinsic raltegravir. To establish an appropriate dosing regimen, an integrated maternal–neonatal pharmacokinetics model was built to predict raltegravir plasma concentrations in neonates with in utero raltegravir exposure. Postnatal age and body weight were used as structural covariates. The model predicted rising or decreasing neonatal elimination profiles based on the time of maternal drug administration relative to time of birth and degree of in utero drug disposition into the central and peripheral compartments. Based on this model, it is recommended to delay the first oral dose of raltegravir until 1–2 days of age in those neonates born to mothers who received raltegravir during pregnancy, labor, and delivery. John Wiley and Sons Inc. 2019-07-10 2019-09 /pmc/articles/PMC6765695/ /pubmed/31215170 http://dx.doi.org/10.1002/psp4.12443 Text en © 2019 Merck Sharp & Dohme Corp and Whitehouse Station. 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
Lommerse, Jos
Clarke, Diana
Kerbusch, Thomas
Merdjan, Henri
Witjes, Han
Teppler, Hedy
Mirochnick, Mark
Acosta, Edward P.
Wenning, Larissa
Nachman, Sharon
Chain, Anne
Maternal–Neonatal Raltegravir Population Pharmacokinetics Modeling: Implications for Initial Neonatal Dosing
title Maternal–Neonatal Raltegravir Population Pharmacokinetics Modeling: Implications for Initial Neonatal Dosing
title_full Maternal–Neonatal Raltegravir Population Pharmacokinetics Modeling: Implications for Initial Neonatal Dosing
title_fullStr Maternal–Neonatal Raltegravir Population Pharmacokinetics Modeling: Implications for Initial Neonatal Dosing
title_full_unstemmed Maternal–Neonatal Raltegravir Population Pharmacokinetics Modeling: Implications for Initial Neonatal Dosing
title_short Maternal–Neonatal Raltegravir Population Pharmacokinetics Modeling: Implications for Initial Neonatal Dosing
title_sort maternal–neonatal raltegravir population pharmacokinetics modeling: implications for initial neonatal dosing
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6765695/
https://www.ncbi.nlm.nih.gov/pubmed/31215170
http://dx.doi.org/10.1002/psp4.12443
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