Hypothesis for a partially non urinary elimination of tranexamic acid in haemorrhagic caesarean section: Traces pilot pharmacokinetic study: Pharmacokinetics of tranexamic acid in obstetrics.
Caesarean section
Intravenous
Pharmacokinetics
Postpartum haemorrhage
Tranexamic acid
Journal
European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences
ISSN: 1879-0720
Titre abrégé: Eur J Pharm Sci
Pays: Netherlands
ID NLM: 9317982
Informations de publication
Date de publication:
01 Oct 2020
01 Oct 2020
Historique:
received:
02
12
2019
revised:
19
07
2020
accepted:
20
07
2020
pubmed:
28
7
2020
medline:
22
6
2021
entrez:
28
7
2020
Statut:
ppublish
Résumé
In previous studies, the choice of doses of tranexamic acid was empirically defined as no pharmacokinetic study had been conducted in haemorrhagic caesarean section. The objective was to build a pharmacokinetic model in patients receiving a single 0.5, 1 or 2 g intravenous bolus. A preliminary monocentric open study was performed in the Lille centre. Blood samples and one urinary sample were collected in the 6 h following the injection. Nine patients were included. Tranexamic acid concentration was measured using liquid chromatography system coupled with tandem mass spectrometry. We used Monolix 2019R1 for population pharmacokinetic modelling. A structural model was constructed followed by the investigation of potential covariates. Data were best described with a two-compartment model with a double first-order elimination from the central compartment. The model was improved when the variable ideal weight per dose was affected as a covariate for the apparent volume of distribution. Assuming a dose of 1 g and a height of 160 cm, the pharmacokinetic parameters were estimated at 10.26 L.h The population pharmacokinetic model of tranexamic acid in haemorrhagic caesarean section was successfully established in our tiny sample of patients. The results of this preliminary TRACES pharmacokinetic study suggested that elimination of tranexamic acid is partially non urinary in contrast with healthy patients.
Sections du résumé
BACKGROUND
BACKGROUND
In previous studies, the choice of doses of tranexamic acid was empirically defined as no pharmacokinetic study had been conducted in haemorrhagic caesarean section.
OBJECTIVE
OBJECTIVE
The objective was to build a pharmacokinetic model in patients receiving a single 0.5, 1 or 2 g intravenous bolus.
METHOD
METHODS
A preliminary monocentric open study was performed in the Lille centre. Blood samples and one urinary sample were collected in the 6 h following the injection. Nine patients were included. Tranexamic acid concentration was measured using liquid chromatography system coupled with tandem mass spectrometry. We used Monolix 2019R1 for population pharmacokinetic modelling. A structural model was constructed followed by the investigation of potential covariates.
RESULTS
RESULTS
Data were best described with a two-compartment model with a double first-order elimination from the central compartment. The model was improved when the variable ideal weight per dose was affected as a covariate for the apparent volume of distribution. Assuming a dose of 1 g and a height of 160 cm, the pharmacokinetic parameters were estimated at 10.26 L.h
CONCLUSIONS
CONCLUSIONS
The population pharmacokinetic model of tranexamic acid in haemorrhagic caesarean section was successfully established in our tiny sample of patients. The results of this preliminary TRACES pharmacokinetic study suggested that elimination of tranexamic acid is partially non urinary in contrast with healthy patients.
Identifiants
pubmed: 32717429
pii: S0928-0987(20)30275-X
doi: 10.1016/j.ejps.2020.105486
pii:
doi:
Substances chimiques
Tranexamic Acid
6T84R30KC1
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
105486Informations de copyright
Copyright © 2020 Elsevier B.V. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of Competing Interest The authors declare no competing interest.