REDUCED PRODUCTION, ABSORPTION, AND ELIMINATION OF ERYTHROPOIETIN IN UREMIA COMPARED WITH HEALTHY-VOLUNTEERS

The purpose of this study was to investigate the metabolism of erythro poietin (EPO) in uremia compared with healthy subjects. Twenty-one pat ients (nine men and 12 women) with end-stage renal failure and anemia and 12 healthy volunteers (3 women and nine men) were studied. The pha rmacokinetic parameters were calculated after an iv and a femoral sc i njection of 100 U/kg of recombinant human EPO. The serum EPO (s-EPO) w as measured by radioimmunoassay at regular intervals until 48 h (iv) a nd 120 h (sc). In uremia, the median terminal elimination half-life wa s significantly longer (8.31 versus 4.92 h; P < 0.001) and the clearan ce was reduced (5.00 versus 7.88 mL/min per 1.73 m(2); P < 0.01). The volume of distribution was (3.70 versus 3.31 L/1.73 m(2)) not signific ant. The estimated endogenous EPO production was significantly lower i n uremia (146 versus 290 U/day per 1.73 m(2); P < 0.001). After sc adm inistration, the bioavailability was significantly lower in the patien ts (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(l5.4 versus 11.0 h; P < 0.02), but the mean input time (sc) was not significantly different (23.3 ver sus 27.8 h). The basal s-EPO was lower in the uremic patients(20.0 ver sus 26.3 U/L; P < 0.05). There was no difference between patients trea ted with hemodialysis and peritoneal dialysis or between uremic men an d women. There was no correlation between the pharmacokinetic paramete rs and age. It was concluded that uremia was associated with a reduced production rate of EPO, a reduced sc bioavailability, and a prolonged elimination of exogenous EPO compared with healthy volunteers. The lo w clearance of EPO in uremia may help to preserve a normal basal level of s-EPO, even in the presence of a reduced production of EPO.