Single-dose pharmacokinetics of recombinant human erythropoietin in patients with various degrees of renal failure.
The pharmacokinetic profile of recombinant human erythropoietin (rHuEpo) was studied after a single intravenous dose of 150 U/kg in ten patients with various degrees of renal function: group I, creatinine clearance greater than 80 ml/min, n = 2; group II, creatinine clearance 10-50 ml/min, n = 6; group III, creatinine clearance less than 3 ml/min (patients undergoing haemodialysis) n = 2. Erythropoietin concentrations in serum and urine samples obtained over 48 h were measured by RIA. rHuEpo was cleared from circulation in an exponential fashion, the half-life ranged from 6.5 to 12.7 h (mean 9.03 h) and was not different between the groups. The apparent volume of distribution varied from 0.041 to 0.099 l/kg (mean 0.070 l/kg) this corresponds to 1.5 times the plasma volume and was unrelated to kidney function. Renal clearance (groups I, II) accounted for less than 3% of total body clearance, both parameters were unaffected by decreasing renal function. These results indicate that, in accordance with animal data, the elimination of rHuEpo occurs mainly through non-renal mechanisms.
Kindler
J
J
Department of Internal Medicine II, RWTH Aachen, Switzerland.
Eckardt
K U
KU
Ehmer
B
B
Jandeleit
K
K
Kurtz
A
A
Schreiber
A
A
Scigalla
P
P
Sieberth
H G
HG
D000328:Adult; D000368:Aged; D004305:Dose-Response Relationship, Drug; D004921:Erythropoietin / Q000008:administration & dosage / Q000493:pharmacokinetics*; D005260:Female; D005919:Glomerular Filtration Rate; D006801:Humans; D007275:Injections, Intravenous; D007676:Kidney Failure, Chronic / Q000097:blood* / Q000628:therapy; D007677:Kidney Function Tests; D008297:Male; D008875:Middle Aged; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000493:pharmacokinetics
D011994:Recombinant Proteins; D004921:Erythropoietin