The pharmacokinetic profile of recombinant human erythropoietin is unchanged in patients undergoing cardiac surgery.
BACKGROUND
In anticipation of future studies, we examined the pharmacokinetics profile of erythropoietin (EPO) in patients undergoing cardiac surgery.


METHODS
Cardiac surgical patients were enrolled into one of six groups: four cardiopulmonary bypass (CPB) groups [placebo (n = 6), 250 IU/kg EPO (n = 3), 500 IU/kg EPO (n = 3), and 500 IU/kg EPO, two doses (n = 6)] and two off-pump coronary artery bypass (OPCAB) groups [placebo (n = 3) and 500 IU/kg EPO (n = 3)]. The EPO was administered prior to anesthesia and 10 min after CPB (if required). Blood samples for serum EPO were collected at baseline, 10 min after dosing, 5 min after sternotomy, during CPB or the equivalent for OPCAB (5, 15, 45, 60 min), and post-CPB (5, 15, 45, and 60 min, 6, 12 and 24 h, and daily until day 5).


RESULTS
Endogenous EPO increased within 24 h of surgery in the placebo group and remained elevated. There was approximately a 40% decrease in serum EPO concentration at the initiation of CPB due to an increase in circulatory blood volume. There were no differences in apparent volume of distribution in the plasma (Vc) (42.2 +/- 9.9, 39.8 +/- 6.3, 42.3 +/- 14.0 mL/kg), clearance (CL) (4.63 +/- 1.14, 3.44 +/- 0.68, 4.27 +/- 0.52 mL h/kg), and t((1/2)) (16.4 +/- 8.0 16.9 +/- 10.6, 22.4 +/- 9.3 h) between the CPB treatment groups. The pharmacokinetic profile of EPO in the OPCAB group was similar to that for the CPB groups: Vc = 39.3 +/- 7.0 mL/kg, CL = 4.98 +/- 0.17 mL h/kg and t((1/2)) = 17.1 +/- 18.1 h.


CONCLUSIONS
CPB had no apparent effect on the pharmacokinetics of EPO.
McCluskey
Stuart A
SA
Department of Anesthesia and Pain Management, Toronto General Hospital, University Health Network, Eaton North 3-405, 200 Elizabeth Street, Toronto, ON M5G 2C4, Canada. stuart.mccluskey@uhn.on.ca
Cheung
Wing K
WK
Katznelson
Rita
R
Poonawala
Humara
H
Fedorko
Ludwik
L
Djaiani
George
G
Mehta
Bobby
B
Karkouti
Keyvan
K
D000368:Aged; D019540:Area Under Curve; D002315:Cardiopulmonary Bypass; D047549:Coronary Artery Bypass, Off-Pump; D004921:Erythropoietin / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D005260:Female; D006207:Half-Life; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D011446:Prospective Studies; D011994:Recombinant Proteins
D011994:Recombinant Proteins; D004921:Erythropoietin