Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Gilliot, Sixtine, Ducloy-Bouthors, Anne-Sophie, Loingeville, Florence, Hennart, Benjamin, Allorge, Delphine, Lebuffe, Gilles, Odou, Pascal
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
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
_version_ 1784675612571467776
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
work_keys_str_mv AT gilliotsixtine pharmacokineticsofcurativetranexamicacidinparturientsundergoingcesareandelivery
AT ducloybouthorsannesophie pharmacokineticsofcurativetranexamicacidinparturientsundergoingcesareandelivery
AT loingevilleflorence pharmacokineticsofcurativetranexamicacidinparturientsundergoingcesareandelivery
AT hennartbenjamin pharmacokineticsofcurativetranexamicacidinparturientsundergoingcesareandelivery
AT allorgedelphine pharmacokineticsofcurativetranexamicacidinparturientsundergoingcesareandelivery
AT lebuffegilles pharmacokineticsofcurativetranexamicacidinparturientsundergoingcesareandelivery
AT odoupascal pharmacokineticsofcurativetranexamicacidinparturientsundergoingcesareandelivery