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

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.