PHARMACOKINETICS OF TRANEXAMIC ACID DURING CARDIOPULMONARY BYPASS (CPB)

Abstract

Introduction: The antifibrinolytic agent tranexamic acid (TA) decreases bleeding in patients undergoing cardiopulmonary bypass (CPB). [1,2] TA dosing before CPB vary from 10 mg. kg-1 bolus + 1 mg. kg-1 h-1 infusion to 100 mg. kg-1 single bolus. We measured the pharmacokinetic profile of 3 dose regimens of TA during CPB, in a prospective randomized trial. Methods: After ethics committee approval, timed arterial blood samples were obtained from 32 patients undergoing CPB. Patients received one of three loading doses (TA 50 mg/kg, Group I; TA 100 mg/kg, Group II; TA 10 mg/kg, Group III); intravenously over 20 minutes before CPB. In addition Group III patients received an infusion of 1 mg.kg-1 h-1 for 10 hours. Plasma concentration of TA was analyzed by ultrafiltration, derivatization and HPLC. Pharmacokinetic modeling was done using software NONMED. The Schwartz-Bayesian criterion (SBC) was used to determine best fit of increasingly complex compartmental models. Results are given as mean +/- SEM. Results: Patient demographics are presented in Table 1Table 1Peak plasma concentrations were higher in groups I and II than in group III by factors of 5 and 10 respectively. Plasma concentrations of TA declined in all groups but the infusion in Group III did not maintain plasma concentrations at a stable value (Figure 1). CPB TA concentration in groups I and II only were able to be modeled by a 2-commpartment model. (V1:10.6 +/- 0.74 L; V2: 11.1 +/- 1.3 L; Cl1: 0.11 +/- 0.03 L/min; Cl2: 0.32 +/- 0.06 L/min; Terminal T1/2 154 min. (V = Volume of distribution, Cl = Clearance)Figure 1Discussion: High dose TA (50 mg/kg and 100 mg/kg) is associated with higher peak plasma concentrations and more stable plasma concentrations during CPB than low dose TA with infusion, which may not be in therapeutic plasma concentration (10-15 mg/L).