Academic Journal
Factors Influencing Unfractionated Heparin Pharmacokinetics and Pharmacodynamics During a Cardiopulmonary Bypass
| العنوان: | Factors Influencing Unfractionated Heparin Pharmacokinetics and Pharmacodynamics During a Cardiopulmonary Bypass |
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| المؤلفون: | Gibert, A, Lanoiselée, Julien, Gouin-Thibault, Isabelle, Pontis, Adeline, Azarnoush, Kasra, Petrosyan, Andranik, Grand, Nathalie, Molliex, Serge, Morel, Jérome, Gergelé, Laurent, Hodin, Sophie, Bin, Valérie, Chaux, Robin, Delavenne, Xavier, Ollier, Edouard |
| المساهمون: | Biologie Intégrative du Tissu Osseux (LBTO), Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Universitaire de Saint-Etienne CHU Saint-Etienne (CHU ST-E), Institut de recherche en santé, environnement et travail (Irset), Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique EHESP (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes (Biosit : Biologie - Santé - Innovation Technologique), Centre Hospitalier Universitaire de Rennes CHU Rennes = Rennes University Hospital Pontchaillou |
| المصدر: | ISSN: 0312-5963. |
| بيانات النشر: | CCSD Springer Verlag |
| سنة النشر: | 2024 |
| المجموعة: | Université Jean Monnet – Saint-Etienne: HAL |
| مصطلحات موضوعية: | [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie |
| الوصف: | International audience ; Background: Unfractionated heparin (UFH) is commonly used during cardiac surgery with a cardiopulmonary bypass to prevent blood clotting. However, empirical administration of UFH leads to variable responses. Pharmacokinetic and pharmacodynamic modeling can be used to optimize UFH dosing and perform real-time individualization. In previous studies, many factors that could influence UFH pharmacokinetics/pharmacodynamics had not been taken into account such as hemodilution or the type of UFH. Few covariates were identified probably owing to a lack of statistical power. This study aims to address these limitations through a meta-analysis of individual data from two studies.Methods: An individual patient data meta-analysis was conducted using data from two single-center prospective observational studies, where different UFH types were used for anticoagulation. A pharmacodynamic/pharmacodynamic model of UFH was developed using a non-linear mixed-effects approach. Time-varying covariates such as hemodilution and fluid infusions during a cardiopulmonary bypass were considered.Results: Activities of UFH's anti-activated factor/anti-thrombin were best described by a two-compartment model. Unfractionated heparin clearance was influenced by body weight and the specific UFH type. Volume of distribution was influenced by body weight and pre-operative fibrinogen levels. Pharmacodynamic data followed a log-linear model, accounting for the effect of hemodilution and the pre-operative fibrinogen level. Equations were derived from the model to personalize UFH dosing based on the targeted activated clotting time level and patient covariates.Conclusions: The population model effectively characterized UFH's pharmacokinetics/pharmacodynamics in cardiopulmonary bypass patients. This meta-analysis incorporated new covariates related to UFH's pharmacokinetics/pharmacodynamics, enabling personalized dosing regimens. The proposed model holds potential for individualization using a Bayesian estimation. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| Relation: | info:eu-repo/semantics/altIdentifier/pmid/38169065; PUBMED: 38169065 |
| DOI: | 10.1007/s40262-023-01334-3 |
| الاتاحة: | https://hal.science/hal-04387601 https://doi.org/10.1007/s40262-023-01334-3 |
| رقم الانضمام: | edsbas.4B8243DC |
| قاعدة البيانات: | BASE |
| DOI: | 10.1007/s40262-023-01334-3 |
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