Evaluating Tranexamic Acid Dosing Strategies for Postpartum Hemorrhage: A Population Pharmacokinetic Approach in Pregnant Individuals

Allison Dunn, Center for Translational Medicine, University of Maryland School of Pharmacy, Baltimore, MD, USA.
Mina Felfeli, Department of Obstetrics and Gynecology, The George Washington University School of Medicine and Health Sciences, Washington, DC, USA.
Sebastian M. Seifert, Department of Anesthesiology, Perioperative and Pain Medicine, Brigham & Women's Hospital, Harvard Medical School, Boston, MA, USA.
Sixtine Gilliot, GRITA - Groupe de Rec, herche sur les formes Injectables et les Technologies Associées, Université de Lille, Lille, France.
Anne-Sophie Ducloy-Bouthors, GRITA - Groupe de Rec, herche sur les formes Injectables et les Technologies Associées, Université de Lille, Lille, France.
Haleem Shakur-Still, Clinical Trials Unit, London School of Hygiene & Tropical Medicine, London, UK.
Amber Geer, Département de Biotechnologie de la Santé, Université Paris-Saclay, UVSQ, INSERM, Infection et Inflammation (2I), Montigny le Bretonneux, France.
Stanislas Grassin-Delyle, Département de Biotechnologie de la Santé, Université Paris-Saclay, UVSQ, INSERM, Infection et Inflammation (2I), Montigny le Bretonneux, France.
Naomi L. Luban, Department of Pediatrics George Washington University, Division of Pediatric Hematology, Children's National Hospital, Washington, DC, USA.
Johannes N. van den Anker, Division of Clinical Pharmacology, Children's National Hospital, Washington, DC, USA.
Jogarao V. Gobburu, Center for Translational Medicine, University of Maryland School of Pharmacy, Baltimore, MD, USA.
Ian Roberts, Clinical Trials Unit, London School of Hygiene & Tropical Medicine, London, UK.
Homa K. Ahmadzia, Department of Obstetrics and Gynecology, Division of Maternal-Fetal Medicine, The George Washington University School of Medicine and Health Science, Washington, DC, USA.

Document Type

Journal Article

Publication Date

5-19-2025

Journal

Journal of clinical pharmacology

DOI

10.1002/jcph.70031

Keywords

modeling; pharmacokinetics; postpartum hemorrhage; simulation; tranexamic acid

Abstract

Tranexamic acid (TXA) is used for the treatment and occasionally prevention of postpartum hemorrhage (PPH); however, questions still remain regarding dosing regimen optimization. This study evaluated TXA pharmacokinetic (PK) data from four clinical trials (NCT: 04274335, 03287336, 00872469, and 02797119) conducted in pregnant participants receiving intravenous, intramuscular, or oral TXA to prevent or treat PPH. The goal of this analysis was to comprehensively characterize TXA PK in a large, heterogeneous population of pregnant individuals to (1) assess the need for weight-based dosing and (2) compare exposure target attainment for alternative routes of administration. A population PK analysis was performed using nonlinear mixed-effects modeling in Pumas, and a stepwise approach was implemented to select the structural model and identify significant covariates. A total of 211 pregnant participants who received between 0.35 and 4 g of TXA intravenously, orally, or intramuscularly offered 1303 TXA plasma concentrations for model development. A two-compartment model with first-order elimination and first-order absorption for both intramuscular and oral administration best described the disposition of TXA. Actual body weight was the only statistically significant covariate identified, but inclusion into the model did not explain a substantial amount of the observed variability. Simulations of virtual pregnant individuals indicated minimal differences in TXA exposure between fixed and weight-based dosing regimens, supporting the use of fixed dosing. Intramuscular TXA was additionally found to be a viable alternative to intravenous administration, achieving similar target exposure metrics.

Department

School of Medicine and Health Sciences Resident Works

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