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Pharmacokinetics of Curative Tranexamic Acid in Parturients Undergoing Cesarean Delivery
The aim of this study was to evaluate the population pharmacokinetics of tranexamic acid (TXA) administered intravenously at a single dose of 0.5 or 1 g in parturients undergoing active hemorrhagic cesarean delivery and to evaluate the influence of patient variables on TXA pharmacokinetics. Subjects...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8952437/ https://www.ncbi.nlm.nih.gov/pubmed/35335955 http://dx.doi.org/10.3390/pharmaceutics14030578 |
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author | Gilliot, Sixtine Ducloy-Bouthors, Anne-Sophie Loingeville, Florence Hennart, Benjamin Allorge, Delphine Lebuffe, Gilles Odou, Pascal |
author_facet | Gilliot, Sixtine Ducloy-Bouthors, Anne-Sophie Loingeville, Florence Hennart, Benjamin Allorge, Delphine Lebuffe, Gilles Odou, Pascal |
author_sort | Gilliot, Sixtine |
collection | PubMed |
description | The aim of this study was to evaluate the population pharmacokinetics of tranexamic acid (TXA) administered intravenously at a single dose of 0.5 or 1 g in parturients undergoing active hemorrhagic cesarean delivery and to evaluate the influence of patient variables on TXA pharmacokinetics. Subjects from three recruiting centers were included in this PK sub-study if randomized in the experimental group (i.v TXA 0.5 g or 1 g over one minute) of the TRACES study. Blood samples and two urinary samples were collected within 6 h after TXA injection. Parametric non-linear mixed-effect modeling (Monolix v2020R1) was computed. The final covariate model building used 315 blood and 117 urinary concentrations from seventy-nine patients. A two-compartment model with a double first-order elimination from the central compartment best described the data. The population estimates of clearance (CL), central volume of distribution (V1), and half-life for a typical 70 kg patient with an estimated renal clearance of 150 mL/min (Cockroft–Gault) were 0.14 L/h, 9.25 L, and 1.8 h. A correlation between estimated creatinine clearance and CL, body weight before pregnancy, and V1 was found and partly explained the PK variability. The final model was internally validated using a 500-run bootstrap. The first population pharmacokinetic model of TXA in active hemorrhagic caesarean section was successfully developed and internally validated. |
format | Online Article Text |
id | pubmed-8952437 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-89524372022-03-26 Pharmacokinetics of Curative Tranexamic Acid in Parturients Undergoing Cesarean Delivery Gilliot, Sixtine Ducloy-Bouthors, Anne-Sophie Loingeville, Florence Hennart, Benjamin Allorge, Delphine Lebuffe, Gilles Odou, Pascal Pharmaceutics Article The aim of this study was to evaluate the population pharmacokinetics of tranexamic acid (TXA) administered intravenously at a single dose of 0.5 or 1 g in parturients undergoing active hemorrhagic cesarean delivery and to evaluate the influence of patient variables on TXA pharmacokinetics. Subjects from three recruiting centers were included in this PK sub-study if randomized in the experimental group (i.v TXA 0.5 g or 1 g over one minute) of the TRACES study. Blood samples and two urinary samples were collected within 6 h after TXA injection. Parametric non-linear mixed-effect modeling (Monolix v2020R1) was computed. The final covariate model building used 315 blood and 117 urinary concentrations from seventy-nine patients. A two-compartment model with a double first-order elimination from the central compartment best described the data. The population estimates of clearance (CL), central volume of distribution (V1), and half-life for a typical 70 kg patient with an estimated renal clearance of 150 mL/min (Cockroft–Gault) were 0.14 L/h, 9.25 L, and 1.8 h. A correlation between estimated creatinine clearance and CL, body weight before pregnancy, and V1 was found and partly explained the PK variability. The final model was internally validated using a 500-run bootstrap. The first population pharmacokinetic model of TXA in active hemorrhagic caesarean section was successfully developed and internally validated. MDPI 2022-03-06 /pmc/articles/PMC8952437/ /pubmed/35335955 http://dx.doi.org/10.3390/pharmaceutics14030578 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Gilliot, Sixtine Ducloy-Bouthors, Anne-Sophie Loingeville, Florence Hennart, Benjamin Allorge, Delphine Lebuffe, Gilles Odou, Pascal Pharmacokinetics of Curative Tranexamic Acid in Parturients Undergoing Cesarean Delivery |
title | Pharmacokinetics of Curative Tranexamic Acid in Parturients Undergoing Cesarean Delivery |
title_full | Pharmacokinetics of Curative Tranexamic Acid in Parturients Undergoing Cesarean Delivery |
title_fullStr | Pharmacokinetics of Curative Tranexamic Acid in Parturients Undergoing Cesarean Delivery |
title_full_unstemmed | Pharmacokinetics of Curative Tranexamic Acid in Parturients Undergoing Cesarean Delivery |
title_short | Pharmacokinetics of Curative Tranexamic Acid in Parturients Undergoing Cesarean Delivery |
title_sort | pharmacokinetics of curative tranexamic acid in parturients undergoing cesarean delivery |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8952437/ https://www.ncbi.nlm.nih.gov/pubmed/35335955 http://dx.doi.org/10.3390/pharmaceutics14030578 |
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