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

Background: epsilon-Aminocaproic acid (EACA) is commonly infused during car diac surgery using empiric dosing schemes. The authors developed a pharmaco kinetic model for EACA elimination in surgical patients, tested whether adj ustments 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 re ceived one of two loading doses of EACA, 30 mg/kg (group I, n = 7) or 100 m g/kg (group LI, n = 6) after CPB, or (group III) a 100 mg/kg loading dose b efore 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 EA CA in the manner of group IU, Blood concentrations of EACA measured by high -performance liquid chromatography, were subjected to mixed-effects pharmac okinetic modeling, Results: The EACA concentration data were best fit by a model with two comp artments 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 varie d 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 aft er CPB. Tno patients with renal failure demonstrated markedly reduced clear ance. 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/m l. Conclusions: EACA clearance declines and volume of distribution increases d uring CPB, The authors' model predicts that more stable perioperative EACA concentrations would be obtained with a smaller lending dose (50 mg/kg give n over 20 min) and a more rapid maintenance infusion (25 mg . kg(-1) . h(-1 )) than are typically employed.