Population Pharmacokinetics and Pharmacodynamics of Tranexamic Acid in Women Undergoing Cesarean Delivery

Aims Population pharmacokinetics (PK) and pharmacodynamics (PD) of tranexamic acid (TXA) have not been studied to prevent postpartum hemorrhage (PPH) in pregnant women. It is unclear which TXA dose assures sufficient PPH prevention. This study investigated population PK/PD of TXA in pregnant women who underwent cesarean delivery to determine the optimal prophylactic doses of TXA for future studies. Methods We analyzed concentration (PK) and maximum lysis (PD) data from 30 pregnant women scheduled for cesarean delivery who received 5 mg/kg, 10 mg/kg, or 15 mg/kg of TXA intravenously, using population approach. Results TXA PK was best described by a two-compartment model with first-order elimination and the following parameters: clearance (between-subject variability) of 9.4 L/hr (27.7%), central volume of 10.1 L (47.4%), inter-compartmental clearance of 22.4 L/hr (66.7%), peripheral volume of 14.0 L (13.1%), and additive error of 1.4 mg/L. The relationship between TXA concentration and maximum lysis was characterized by a sigmoid Emax model with baseline lysis of 97%, maximum inhibition of 89%, IC50 of 6.0 mg/L (65.3%), hill factor of 8.5 (86.3%), and additive error of 7.3%. Simulations demonstrated that 500 mg and 650 mg of TXA maintained therapeutic targets for 30 minutes and 1 hour respectively in 90% of patients. Conclusion This is the first population PK and PD study of TXA in pregnant women undergoing cesarean delivery. Our analysis suggests that a 650 mg dose provides adequate PPH prophylaxis up to 1 hour, which is less than the currently used 1000 mg of TXA in pregnant women.