Simulation-based suggestions to improve ibuprofen dosing for patent ductus arteriosus in preterm newborns

PURPOSE: Ibuprofen is the drug of choice for treatment of patent ductus arteriosus (PDA). There is accumulating evidence that current ibuprofen-dosing regimens for PDA treatment are inadequate. We aimed to propose an improved dosing regimen, based on all current knowledge. METHODS: We performed a li...

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Autores principales: Flint, Robert B., ter Heine, Rob, Spaans, Edwin, Burger, David M., de Klerk, Johan C. A., Allegaert, Karel, Knibbe, Catherijne A. J., Simons, Sinno H. P.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer Berlin Heidelberg 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6244763/
https://www.ncbi.nlm.nih.gov/pubmed/30054639
http://dx.doi.org/10.1007/s00228-018-2529-y
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author Flint, Robert B.
ter Heine, Rob
Spaans, Edwin
Burger, David M.
de Klerk, Johan C. A.
Allegaert, Karel
Knibbe, Catherijne A. J.
Simons, Sinno H. P.
author_facet Flint, Robert B.
ter Heine, Rob
Spaans, Edwin
Burger, David M.
de Klerk, Johan C. A.
Allegaert, Karel
Knibbe, Catherijne A. J.
Simons, Sinno H. P.
author_sort Flint, Robert B.
collection PubMed
description PURPOSE: Ibuprofen is the drug of choice for treatment of patent ductus arteriosus (PDA). There is accumulating evidence that current ibuprofen-dosing regimens for PDA treatment are inadequate. We aimed to propose an improved dosing regimen, based on all current knowledge. METHODS: We performed a literature search on the clinical pharmacology and effectiveness of ibuprofen. (R)- and (S)-ibuprofen plasma concentration-time profiles of different dosing regimens were simulated using a population pharmacokinetic model and evaluated to obtain a safe, yet likely more efficacious ibuprofen exposure. RESULTS: The most effective intravenous ibuprofen dosing in previous clinical trials included a first dose of 20 mg kg(−1) followed by 10 mg kg(−1) every 24 h. Simulations of this dosing regimen show an (S)-ibuprofen trough concentration of 43 mg L(−1) is reached at 48 h, which we assumed the target through concentration. We show that this target can be reached with a first dose of 18 mg kg(−1), followed by 4 mg kg(−1) every 12 h. After 96 h postnatal age, the dose should be increased to 5 mg kg(−1) every 12 h due to maturation of clearance. This twice-daily dosing has the advantage over once-daily dosing that an effective trough level may be maintained, while peak concentrations are substantially (22%) lower. CONCLUSIONS: We propose to improve intermittent ibuprofen-dosing regimens by starting with a high first dose followed by a twice-daily maintenance dosing regimen that requires increase over time and should be continued until sufficient effect has been achieved. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00228-018-2529-y) contains supplementary material, which is available to authorized users.
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spelling pubmed-62447632018-12-04 Simulation-based suggestions to improve ibuprofen dosing for patent ductus arteriosus in preterm newborns Flint, Robert B. ter Heine, Rob Spaans, Edwin Burger, David M. de Klerk, Johan C. A. Allegaert, Karel Knibbe, Catherijne A. J. Simons, Sinno H. P. Eur J Clin Pharmacol Pharmacokinetics and Disposition PURPOSE: Ibuprofen is the drug of choice for treatment of patent ductus arteriosus (PDA). There is accumulating evidence that current ibuprofen-dosing regimens for PDA treatment are inadequate. We aimed to propose an improved dosing regimen, based on all current knowledge. METHODS: We performed a literature search on the clinical pharmacology and effectiveness of ibuprofen. (R)- and (S)-ibuprofen plasma concentration-time profiles of different dosing regimens were simulated using a population pharmacokinetic model and evaluated to obtain a safe, yet likely more efficacious ibuprofen exposure. RESULTS: The most effective intravenous ibuprofen dosing in previous clinical trials included a first dose of 20 mg kg(−1) followed by 10 mg kg(−1) every 24 h. Simulations of this dosing regimen show an (S)-ibuprofen trough concentration of 43 mg L(−1) is reached at 48 h, which we assumed the target through concentration. We show that this target can be reached with a first dose of 18 mg kg(−1), followed by 4 mg kg(−1) every 12 h. After 96 h postnatal age, the dose should be increased to 5 mg kg(−1) every 12 h due to maturation of clearance. This twice-daily dosing has the advantage over once-daily dosing that an effective trough level may be maintained, while peak concentrations are substantially (22%) lower. CONCLUSIONS: We propose to improve intermittent ibuprofen-dosing regimens by starting with a high first dose followed by a twice-daily maintenance dosing regimen that requires increase over time and should be continued until sufficient effect has been achieved. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00228-018-2529-y) contains supplementary material, which is available to authorized users. Springer Berlin Heidelberg 2018-07-28 2018 /pmc/articles/PMC6244763/ /pubmed/30054639 http://dx.doi.org/10.1007/s00228-018-2529-y Text en © The Author(s) 2018 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.
spellingShingle Pharmacokinetics and Disposition
Flint, Robert B.
ter Heine, Rob
Spaans, Edwin
Burger, David M.
de Klerk, Johan C. A.
Allegaert, Karel
Knibbe, Catherijne A. J.
Simons, Sinno H. P.
Simulation-based suggestions to improve ibuprofen dosing for patent ductus arteriosus in preterm newborns
title Simulation-based suggestions to improve ibuprofen dosing for patent ductus arteriosus in preterm newborns
title_full Simulation-based suggestions to improve ibuprofen dosing for patent ductus arteriosus in preterm newborns
title_fullStr Simulation-based suggestions to improve ibuprofen dosing for patent ductus arteriosus in preterm newborns
title_full_unstemmed Simulation-based suggestions to improve ibuprofen dosing for patent ductus arteriosus in preterm newborns
title_short Simulation-based suggestions to improve ibuprofen dosing for patent ductus arteriosus in preterm newborns
title_sort simulation-based suggestions to improve ibuprofen dosing for patent ductus arteriosus in preterm newborns
topic Pharmacokinetics and Disposition
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6244763/
https://www.ncbi.nlm.nih.gov/pubmed/30054639
http://dx.doi.org/10.1007/s00228-018-2529-y
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