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...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-03-01
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| Series: | Pharmaceutics |
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| Online Access: | https://www.mdpi.com/1999-4923/14/3/578 |
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| author | Sixtine Gilliot Anne-Sophie Ducloy-Bouthors Florence Loingeville Benjamin Hennart Delphine Allorge Gilles Lebuffe Pascal Odou |
| author_facet | Sixtine Gilliot Anne-Sophie Ducloy-Bouthors Florence Loingeville Benjamin Hennart Delphine Allorge Gilles Lebuffe Pascal Odou |
| author_sort | Sixtine Gilliot |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-03-09T12:58:43Z |
| format | Article |
| id | doaj.art-50a1c8061a3a432fb4e35dc3ce27dccf |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-09T12:58:43Z |
| publishDate | 2022-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-50a1c8061a3a432fb4e35dc3ce27dccf2023-11-30T21:56:54ZengMDPI AGPharmaceutics1999-49232022-03-0114357810.3390/pharmaceutics14030578Pharmacokinetics of Curative Tranexamic Acid in Parturients Undergoing Cesarean DeliverySixtine Gilliot0Anne-Sophie Ducloy-Bouthors1Florence Loingeville2Benjamin Hennart3Delphine Allorge4Gilles Lebuffe5Pascal Odou6ULR-7365-Groupe de Recherche sur les Formes Injectables et les Technologies Associées (GRITA), Université de Lille, Centre Hospitalier Universitaire de Lille, F-59000 Lille, FranceULR-7365-Groupe de Recherche sur les Formes Injectables et les Technologies Associées (GRITA), Université de Lille, Centre Hospitalier Universitaire de Lille, F-59000 Lille, FranceULR2694—METRICS—Evaluation des Technologies de Santé et des Pratiques Médicales, Université de Lille, Centre Hospitalier Universitaire de Lille, F-59000 Lille, FranceUnité Fonctionnelle de Toxicologie, Pôle Biologie Pathologie Génétique, Centre Biologie Pathologie, Centre Hospitalier Universitaire de Lille, F-59000 Lille, FranceUnité Fonctionnelle de Toxicologie, Pôle Biologie Pathologie Génétique, Centre Biologie Pathologie, Centre Hospitalier Universitaire de Lille, F-59000 Lille, FranceULR-7365-Groupe de Recherche sur les Formes Injectables et les Technologies Associées (GRITA), Université de Lille, Centre Hospitalier Universitaire de Lille, F-59000 Lille, FranceULR-7365-Groupe de Recherche sur les Formes Injectables et les Technologies Associées (GRITA), Université de Lille, Centre Hospitalier Universitaire de Lille, F-59000 Lille, FranceThe 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.https://www.mdpi.com/1999-4923/14/3/578caesarean sectionintravenouspharmacokineticspostpartum hemorrhagetranexamic acid |
| spellingShingle | Sixtine Gilliot Anne-Sophie Ducloy-Bouthors Florence Loingeville Benjamin Hennart Delphine Allorge Gilles Lebuffe Pascal Odou Pharmacokinetics of Curative Tranexamic Acid in Parturients Undergoing Cesarean Delivery Pharmaceutics caesarean section intravenous pharmacokinetics postpartum hemorrhage tranexamic acid |
| 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 | caesarean section intravenous pharmacokinetics postpartum hemorrhage tranexamic acid |
| url | https://www.mdpi.com/1999-4923/14/3/578 |
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