Pharmacokinetics of ε-aminocaproic acid in patients undergoing aortocoronary bypass surgery

Background: epsilon-Aminocaproic acid (EACA) is commonly infused during cardiac surgery using empiric dosing schemes. The authors developed a pharmacokinetic model for EACA elimination in surgical patients, tested whether adjustments for cardiopulmonary bypass (CPB) would improve the model, and then used the model to develop an EACA dosing schedule that would yield nearly constant EACA blood concentrations. Methods: Consenting patients undergoing elective coronary artery surgery received one of two loading doses of EACA, 30 mg/kg (group I, n = 7) or 100 mg/kg (group LI, n = 6) after CPB, or (group III) a 100 mg/kg loading dose before BE and a 10 mg . kg(-1) . h(-1) maintenance infusion continued for 4 h during and after CPB (n = 7), Two patients with renal failure received EACA in the manner of group IU, Blood concentrations of EACA measured by high-performance liquid chromatography, were subjected to mixed-effects pharmacokinetic modeling, Results: The EACA concentration data were best fit by a model with two compartments and corrections for CPB, The elimination rate constant k(10) fell from 0.011 before BE to 0.0006 during BE, returning to 0.011 after CPB. V-1 increased 3.8 1 with CPB and remained at that value thereafter. Cl-1 varied from 0.08 1/min before CPB to 0.007 l/min during CPB and 0.13 l/min after BE. Cl-2 increased from 0.09 l/min before CPB to 0.14 l/min during and after CPB. Tno patients with renal failure demonstrated markedly reduced clearance. Using their model, the authors predict that an EACA loading infusion of 50 mg/kg gh en over 20 min and a maintenance infusion of 25 mg . kg(-1) . h(-1) would maintain a nearly constant target concentration of 260 mu g/ml. Conclusions: EACA clearance declines and volume of distribution increases during CPB, The authors' model predicts that more stable perioperative EACA concentrations would be obtained with a smaller lending dose (50 mg/kg given over 20 min) and a more rapid maintenance infusion (25 mg . kg(-1) . h(-1)) than are typically employed.