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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2019-09-01
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Series: | CPT: Pharmacometrics & Systems Pharmacology |
Online Access: | https://doi.org/10.1002/psp4.12443 |
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doaj-e0b66d5f0a014bd788ec368d457eb18d2020-11-25T03:51:31ZengWileyCPT: Pharmacometrics & Systems Pharmacology2163-83062019-09-018964365310.1002/psp4.12443Maternal–Neonatal Raltegravir Population Pharmacokinetics Modeling: Implications for Initial Neonatal DosingJos Lommerse0Diana Clarke1Thomas Kerbusch2Henri Merdjan3Han Witjes4Hedy Teppler5Mark Mirochnick6Edward P. Acosta7Larissa Wenning8Sharon Nachman9Anne Chain10Certara Strategic Consulting Oss The NetherlandsBoston Medical Center Boston Massachusetts USACertara Strategic Consulting Oss The NetherlandsCertara Strategic Consulting Paris FranceCertara Strategic Consulting Oss The NetherlandsMerck & Co., Inc. Upper Gwynedd Pennsylvania USABoston University School of Medicine Boston Massachusetts USAUniversity of Alabama at Birmingham Birmingham Alabama USAMerck & Co., Inc. Upper Gwynedd Pennsylvania USAState University of New York Stony Brook New York USAMerck & Co., Inc. Rahway New Jersey USARaltegravir 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.https://doi.org/10.1002/psp4.12443 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Jos Lommerse Diana Clarke Thomas Kerbusch Henri Merdjan Han Witjes Hedy Teppler Mark Mirochnick Edward P. Acosta Larissa Wenning Sharon Nachman Anne Chain |
spellingShingle |
Jos Lommerse Diana Clarke Thomas Kerbusch Henri Merdjan Han Witjes Hedy Teppler Mark Mirochnick Edward P. Acosta Larissa Wenning Sharon Nachman Anne Chain Maternal–Neonatal Raltegravir Population Pharmacokinetics Modeling: Implications for Initial Neonatal Dosing CPT: Pharmacometrics & Systems Pharmacology |
author_facet |
Jos Lommerse Diana Clarke Thomas Kerbusch Henri Merdjan Han Witjes Hedy Teppler Mark Mirochnick Edward P. Acosta Larissa Wenning Sharon Nachman Anne Chain |
author_sort |
Jos Lommerse |
title |
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_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_sort |
maternal–neonatal raltegravir population pharmacokinetics modeling: implications for initial neonatal dosing |
publisher |
Wiley |
series |
CPT: Pharmacometrics & Systems Pharmacology |
issn |
2163-8306 |
publishDate |
2019-09-01 |
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. |
url |
https://doi.org/10.1002/psp4.12443 |
work_keys_str_mv |
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