Reduced production, absorption, and elimination of erythropoietin in uremia compared with healthy volunteers

The purpose of this study was to investigate the metabolism of erythropoietin (EPO) in uremia compared with healthy subjects. Twenty-one patients (nine men and 12 women) with end-stage renal failure and anemia and 12 healthy volunteers (3 women and nine men) were studied. The pharmacokinetic paramet...

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Bibliographic Details
Published in:Journal of the American Society of Nephrology 1994-08, Vol.5 (2), p.177-185
Main Authors: Jensen, J D, Madsen, J K, Jensen, L W, Pedersen, E B
Format: Article
Language:English
Subjects:
Absorption
Adult
Aged
Biological Availability
Case-Control Studies
Erythropoietin - administration & dosage
Erythropoietin - biosynthesis
Erythropoietin - blood
Erythropoietin - pharmacokinetics
Female
Humans
Injections, Intravenous
Injections, Subcutaneous
Kidney Failure, Chronic - blood
Kidney Failure, Chronic - metabolism
Male
Middle Aged
Peritoneal Dialysis, Continuous Ambulatory
Recombinant Proteins - administration & dosage
Recombinant Proteins - pharmacokinetics
Renal Dialysis
Uremia - blood
Uremia - metabolism
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Summary:The purpose of this study was to investigate the metabolism of erythropoietin (EPO) in uremia compared with healthy subjects. Twenty-one patients (nine men and 12 women) with end-stage renal failure and anemia and 12 healthy volunteers (3 women and nine men) were studied. The pharmacokinetic parameters were calculated after an i.v. and a femoral sc injection of 100 U/kg of recombinant human EPO. The serum EPO (s-EPO) was measured by radio-immunoassay at regular intervals until 48 h (i.v.) and 120 h (sc). In uremia, the median terminal elimination half-life was significantly longer (8.31 versus 4.92 h; P < 0.001) and the clearance was reduced (5.00 versus 7.88 mL/min per 1.73 m2; P < 0.01). The volume of distribution was (3.70 versus 3.31 L/1.73 m2) not significant. The estimated endogenous EPO production was significantly lower in uremia (146 versus 290 U/day per 1.73 m2; P < 0.001). After sc administration, the bioavailability was significantly lower in the patients (23.7 versus 38.5%; P < 0.01), and the maximal s-EPO was lower (113 versus 153 U/L; P < 0.05) and delayed (15.4 versus 11.0 h; P < 0.02), but the mean input time (sc) was not significantly different (23.3 versus 27.8 h). The basal s-EPO was lower in the uremic patients (20.0 versus 26.3 U/L; P < 0.05). There was no difference between patients treated with hemodialysis and peritoneal dialysis or between uremic men and women. There was no correlation between the pharmacokinetic parameters and age.
ISSN:1046-6673
1533-3450
DOI:10.1681/ASN.V52177