PII-077 - POPULATION PHARMACOKINETIC MODELING AND SIMULATION OF TRANEXAMIC ACID IN ADULTS TRAUMA PATIENTS.

G. Stitt¹, P. Spinella², K. Downes³, A. Zuppa³; ¹Children's Hospital of Philadelphia, Philadelphia, PA, USA, ²University of Pittsburgh Medical Center, Pittsburgh, PA, USA, ³Children's Hospital of Philadelphia, Philadelphia, PA, USA.

Background: Tranexamic acid (TXA) is an antifibrinolytic that inhibits plasminogen activation and plasmin activity, but pharmacokinetic (PK) information in trauma patients is limited.

Methods: A population PK (popPK) analysis of the TAMPITI Trial included 94 patients ≥18 yrs with traumatic injury, given ≥1 blood product and/or requiring immediate transfer to the operating room, and could receive TXA in ≤2 hrs from time of injury. Patients were randomized to a single dose of either 2g or 4g. PopPK analysis was conducted NONMEM. Covariates were selected by stepwise/backward elimination. Simulations were performed using the final model to generate estimated plasma TXA concentrations in 1000 subjects. Dosing schemes were tested to achieve a target TXA plasma concentration of ≥10 mg/L 8 hrs after administration of the initial dose.

Results: TXA PK was best described by a 2-compartment model with additive residual error and allometric scaling on all parameters. Serum creatinine, near infrared spectroscopy, and platelet count were significant covariates on clearance, and total transfusion volume on central volume. Based on simulations, a 2g bolus dose repeated 3 hours later best achieved the target (Figure 1).

Conclusion: Based on a popPK model of TXA in adult trauma patients, a 2g bolus at time 0 should be administered and repeated 3 hrs later for patients with ongoing hemorrhage.

Figure 1: Simulated TXA Concentration in Adult Trauma Patients (2g Bolus)