Abstract
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 t½ (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 t½ = 17.1 ± 18.1 h.
Conclusions
CPB had no apparent effect on the pharmacokinetics of EPO.
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Notes
http://www.fda.gov/cder/drug/infopage/RHE/default.htm; accessed 10 Oct 2007
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Acknowledgements
This work would not have been possible without the dedication and organization of Jo Carroll, Manager Clinical Research (University Health Network, University of Toronto, Toronto, ONT, Canada).
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This work was supported by an unrestricted educational grant from Ortho Biotech Canada, a Division of Janssen Ortho Inc. Preliminary data was presented at the Canadian Anesthesiology Society Meeting in June 2004.
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McCluskey, S.A., Cheung, W.K., Katznelson, R. et al. The pharmacokinetic profile of recombinant human erythropoietin is unchanged in patients undergoing cardiac surgery. Eur J Clin Pharmacol 65, 273–279 (2009). https://doi.org/10.1007/s00228-008-0575-6
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DOI: https://doi.org/10.1007/s00228-008-0575-6