The pharmacokinetics of epsilon-aminocaproic acid in children undergoing surgical repair of congenital heart defects.
epsilon-Aminocaproic acid (epsilonACA) 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 epsilonACA concentrations. Eight patients were enrolled in our study. epsilonACA 50 mg/kg was administered three times IV: before, during, and after cardiopulmonary bypass (CPB). Nine serum samples were obtained. epsilonACA 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 (V(1)) adjusted for weight and CPB. Compared with published results in adults, modeling suggests that weight-adjusted V(1) is larger in children than in adults before, during, and after CPB. Clearance from the central compartment (k(10)) was also greater in children than adults, and declined during CPB. Redistribution rates from the central compartment, k(12) and k(21), were greater in children and not affected by CPB. We modeled several different dosing regimens for epsilonACA based on the larger V(1), and higher redistribution and clearance variables. We conclude that, because of the developmental differences in pharmacokinetic variables of epsilonACA, 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.


CONCLUSIONS
Pharmacokinetic modeling of epsilon-aminocaproic acid in children undergoing cardiac surgery suggests that there are developmental differences in pharmacokinetic variables. Based on these data, a dosing modification in children is suggested which may better maintain serum concentrations in children when compared with adults.
Ririe
Douglas G
DG
Department of Anesthesiology, Wake Forest University School of Medicine, Winston-Salem, North Carolina 27157-1009, USA. dririe@wfubmc.edu
James
Robert L
RL
O'Brien
James J
JJ
Lin
Yonggu A
YA
Bennett
Judy
J
Barclay
David
D
Hines
Michael H
MH
Butterworth
John F
JF
D015119:Aminocaproic Acid / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D000768:Anesthesia, General; D002315:Cardiopulmonary Bypass; D002675:Child, Preschool; D005343:Fibrinolytic Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D006330:Heart Defects, Congenital / Q000601:surgery*; D006801:Humans; D007223:Infant
D005343:Fibrinolytic Agents; D015119:Aminocaproic Acid