The Pharmacokinetics of ε-Aminocaproic Acid in Children Undergoing Surgical Repair of Congenital Heart Defects

ε-Aminocaproic acid (εACA) is often administered to children undergoing cardiac surgery by using empiric dosing techniques. We hypothesized that children would have different pharmacokinetic variables and require a dosing scheme different from adults to maintain stable and effective serum εACA concentrations. Eight patients were enrolled in our study. εACA 50 mg/kg was administered three times IVbefore, during, and after cardiopulmonary bypass (CPB). Nine serum samples were obtained. εACA plasma concentrations were measured by using high-performance liquid chromatography, and pharmacokinetic modeling was done by using NONMEM. The best fit was seen with a two-compartment model with volume of distribution (V1) adjusted for weight and CPB. Compared with published results in adults, modeling suggests that weight-adjusted V1 is larger in children than in adults before, during, and after CPB. Clearance from the central compartment (k10) was also greater in children than adults, and declined during CPB. Redistribution rates from the central compartment, k12 and k21, were greater in children and not affected by CPB. We modeled several different dosing regimens for εACA based on the larger V1, and higher redistribution and clearance variables. We conclude that, because of the developmental differences in pharmacokinetic variables of εACA, when compared with adult patients, a larger initial dose and faster infusion rate as well as an addi-tional dose on CPB are needed to maintain similar concentrations.