Gender does not influence epsilon-aminocaproic acid concentrations in adults undergoing cardiopulmonary bypass

Epsilon-aminocaproic acid (epsilon-ACA) is administered to cardiac surgery patients to reduce blood transfusions. Highly water-soluble drugs, such as epsilon-ACA, often have larger distribution volumes in males than in females. We hypothesized that epsilon-ACA concentrations using this dosing scheme would differ by gender because of differences in body composition and weight-adjusted volumes of distribution. Ten men and 10 women undergoing elective coronary artery surgery with cardiopulmonary bypass (CPB) received a 50 mg/kg epsilon-ACA initial dose over 20 min and a 25 mg. kg(-1) x h(-1) epsilon-ACA maintenance infusion for 4 h. The area under the epsilon-ACA arterial concentration versus time curves was compared by using analysis of variance. Measured epsilon-ACA concentrations were smaller than predicted by the published model, but the area under the concentration versus time curves was not significantly different between men and women. Combining the present concentration data with that previously published, our updated two-compartment model included the following estimated population pharmacokinetic values: V(1) (11.8 L pre-CPB, 14.9 L during and after CPB), V(2) (12.0 L pre-CPB, 15.0 L during and after CPB), Cl(1) (0.125 L/min pre-CPB, 0.037 L/min during CPB, 0.156 L/min after CPB), Cl(2) (0.155 L/min pre-CPB, 0.013 L/min during CPB, 0.193 L/min after CPB).