title: The pharmacokinetics and pharmacodynamics of recombinant human erythropoietin in haemodialysis patients.
abstract: 1. The pharmacokinetics of and therapeutic response to recombinant human erythropoietin (rcEPO) were studied in 12 patients under chronic haemodialysis on a thrice weekly intravenous rcEPO treatment scheme. The kinetics of rcEPO were also assessed after a subcutaneous injection during the initial period and during maintenance treatment. RcEPO was measured in plasma by radioimmunoassay. 2. After the first i.v. dose plasma erythropoietin concentrations were best described by a monoexponential disposition function with a mean (+/- s.d.) elimination half-life of 5.4 +/- 1.7 h. The volume of distribution was 70 +/- 5.2 ml kg-1 and the clearance was 10.1 +/- 3.5 ml h-1 kg-1 (n = 12). 3. After 3 months of continuous therapy, the plasma half-life of rcEPO decreased by 15% (P < 0.05, mean half-life during steady state: 4.6 +/- 2.8 h), while mean clearance and volume of distribution remained constant. 4. After the first s.c. injection the mean (+/- s.d.) absorption time was 22 +/- 11 h and systemic availability was 44 +/- 7%. 5. Changes in haemoglobin concentrations were described by a linear additive dose-response model, defined by an efficacy constant (Keff) and the mean erythrocyte lifetime (MRTHb). The sample mean (+/- s.d.) Keff was 0.043 +/- 0.017 g dl-1 Hb per 1000 units rcEPO and MRTHb was 10.02 +/- 1.75 weeks. The net effect of rcEPO treatment was described by the area under the unit-dose-response curve (AUEC) with a mean (+/- s.d.) value of 0.45 +/- 0.23 g dl-1 weeks. 6. RcEPO clearance showed a significant positive correlation (r2 = 0.41) with the effectiveness of rcEPO therapy, as measured by the parameters Keff or AUEC.
authors: Institute of Clinical Pharmacology, Klinikum Steglitz, Free University Berlin, Germany.
authors: J
authors: J
authors: Brockmöller
authors: J
authors: J
authors: Köchling
authors: W
authors: W
authors: Weber
authors: M
authors: M
authors: Looby
authors: I
authors: I
authors: Roots
authors: H H
authors: HH
authors: Neumayer
mesh_terms: D000328:Adult; D000368:Aged; D004906:Erythrocyte Count / Q000187:drug effects; D004921:Erythropoietin / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology*; D005260:Female; D006454:Hemoglobins / Q000032:analysis; D006801:Humans; D008297:Male; D008875:Middle Aged; D011863:Radioimmunoassay; D011994:Recombinant Proteins / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology; D006435:Renal Dialysis; D012156:Reticulocytes / Q000187:drug effects
chemical_list: D006454:Hemoglobins; D011994:Recombinant Proteins; D004921:Erythropoietin