Pharmacokinetics of Epoetin in Dialysis Patients Before and After Correction of the Anaemia

Autor: L. W. Jensen, Jens Madsen, Erling B. Pedersen, Jens Dam Jensen
Rok vydání: 1994
Předmět:
Zdroj: Drug Investigation. 8:278-287
ISSN: 1179-1918
0114-2402
DOI: 10.1007/bf03257440
Popis: Summary The purpose of this study was to investigate the influence of prolonged treat­ ment with recombinant human erythropoietin (epoetin) on the pharmacokinetics of epoetin in dialysis patients. 12 patients (male/female: 6/6, median age 44 years) with end-stage renal failure were investigated. Five were treated with continuous ambulatory peritoneal dialysis and 7 with haemodialysis. The pharmacokinetics were studied in each patient after an intravenous and a subcutaneous dose of epoetin 100 U/kg before regular treatment with epoetin was instituted. The in­ vestigation was repeated in the same patients after a median of 8 months of regular epoetin treatment. The haematocrit count increased from 25 to 33% (medians). The intravenous elimination half-life (8.23 vs 7.96 hours), intravenous mean residence time (ll.S vs 11.2 hours), clearance (0.31 vs 0.32 Llhf1.73 m2), sub­ cutaneous maximal concentration (108 vs 123 U/L) at 19 vs 12 hours, and bio­ availability (20.8 vs 21.6%) did not change significantly after prolonged epoetin treatment. The volume of distribution was slightly reduced from 3.76 to 3.46 LlI.73m2. The estimated absorption half-life (25.1 vs 16.7 hours), the mean input time (29.0 vs 29.9 hours), and the mean residence time (42.5 vs 40.1 hours) after subcutaneous application did not change significantly. The estimated endogenous epoetin production was unchanged at 144 vs ISS U/day/1.73m2. The loss of epoetin in the peritoneal dialysis bags was below 2.3% of the dose. In conclusion, except for a small reduction in the volume of distribution, long term treatment with epoetin had no influence on the intravenous or subcutaneous pharmacokinetics of epoetin in dialysis patients. No compensatory adjustment of the native epoetin production was detected.
Databáze: OpenAIRE
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