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 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.(ABSTRACT TRUNCATED AT 250 WORDS)
Jensen
J D
JD
Department of Nephrology and Medicine C, Skejby Hospital, University Hospital, Aarhus, Denmark.
Madsen
J K
JK
Jensen
L W
LW
Pedersen
E B
EB
D000042:Absorption; D000328:Adult; D000368:Aged; D001682:Biological Availability; D016022:Case-Control Studies; D004921:Erythropoietin / Q000008:administration & dosage / Q000096:biosynthesis / Q000097:blood / Q000493:pharmacokinetics*; D005260:Female; D006801:Humans; D007275:Injections, Intravenous; D007279:Injections, Subcutaneous; D007676:Kidney Failure, Chronic / Q000097:blood / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D010531:Peritoneal Dialysis, Continuous Ambulatory; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000493:pharmacokinetics; D006435:Renal Dialysis; D014511:Uremia / Q000097:blood / Q000378:metabolism*
D011994:Recombinant Proteins; D004921:Erythropoietin