title: The pharmacokinetic profile of recombinant human erythropoietin is unchanged in patients undergoing cardiac surgery.
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 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.
authors.affiliation: 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
authors.forename: Stuart A
authors.initials: SA
authors.lastname: McCluskey
authors.forename: Wing K
authors.initials: WK
authors.lastname: Cheung
authors.forename: Rita
authors.initials: R
authors.lastname: Katznelson
authors.forename: Humara
authors.initials: H
authors.lastname: Poonawala
authors.forename: Ludwik
authors.initials: L
authors.lastname: Fedorko
authors.forename: George
authors.initials: G
authors.lastname: Djaiani
authors.forename: Bobby
authors.initials: B
authors.lastname: Mehta
authors.forename: Keyvan
authors.initials: K
authors.lastname: Karkouti
mesh_terms: 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
chemical_list: D011994:Recombinant Proteins; D004921:Erythropoietin