The impact of renal dysfunction on aprotinin pharmacokinetics during cardiopulmonary bypass.
Aprotinin is a serine protease inhibitor that undergoes metabolism in the kidney. Because elimination is almost entirely renal, the clearance of aprotinin may be reduced in patients with renal insufficiency. Unfortunately, there are no data regarding aprotinin pharmacokinetics in cardiac surgical patients with renal insufficiency or end-stage renal disease (ESRD) undergoing cardiopulmonary bypass (CPB). We, therefore, determined the clearance (ApCl) and elimination half-life (T1/2) of aprotinin in 26 cardiac surgical patients with normal and abnormal renal function (creatinine clearance [CrCl] 0-122 mL/min) undergoing CPB. Subjects were given a 2 million kallikrein inhibiting unit (KIU) initial dose of aprotinin, followed by a 0.25 million KIU/h infusion. No aprotinin was added to the pump prime. Plasma aprotinin concentrations were sampled at 30 min after completion of the loading dose, 30 and 60 min after the onset of CPB, at the end of CPB, and at 8, 24, and 32 h after completion of the loading dose. ApCl was directly related and the elimination T1/2 inversely related to CrCl (r = 0.75 and 0.42, respectively). In patients with a CrCl >50 mL/min, the T1/2 and ApCl were 7.8 h and 53 mL/min, respectively, compared with 19.9 h and 25 mL/min (P < 0.05, P < 0.002, respectively) for patients with ESRD. In conclusion, ApCl is reduced, and T1/2 is prolonged in patients with renal insufficiency or ESRD undergoing CPB. Dosing modifications may be necessary for patients with abnormal renal function undergoing cardiac surgery.


CONCLUSIONS
Because aprotinin is metabolized and eliminated in the kidney, its clearance may be reduced in patients with renal insufficiency. Our data suggest that aprotinin clearance is reduced, and aprotinin half-lives are prolonged in patients with renal insufficiency undergoing CPB. Dosing modification may therefore be indicated when aprotinin is administered to these patients for cardiac surgery.
O'Connor
C J
CJ
Department of Anesthesiology, Rush Medical College, Rush-Presbyterian-St Lukes Medical Center, Chicago, Illinois 60612, USA. coconnor@rpslmc.edu
Brown
D V
DV
Avramov
M
M
Barnes
S
S
O'Connor
H N
HN
Tuman
K J
KJ
D000368:Aged; D007611:Aprotinin / Q000493:pharmacokinetics*; D006348:Cardiac Surgical Procedures; D002315:Cardiopulmonary Bypass; D003404:Creatinine / Q000378:metabolism; D006207:Half-Life; D006490:Hemostatics / Q000493:pharmacokinetics*; D006801:Humans; D007668:Kidney / Q000378:metabolism* / Q000503:physiopathology; D007676:Kidney Failure, Chronic / Q000378:metabolism*; D008875:Middle Aged
D006490:Hemostatics; D007611:Aprotinin; D003404:Creatinine