Pharmacokinetics and pharmacodynamics of subcutaneous and intraperitoneal administration of recombinant human erythropoietin in patients on continuous ambulatory peritoneal dialysis

Kelvin Chan, University of Wolverhampton, United Kingdom

Abstract

The single-dose pharmacokinetics of 50 U/kg body weight of recombinant human erythropoietin (rHuEPO) given by either the subcutaneous (s.c.) or the intraperitoneal (i.p.) route were studied in 20 anemic patients maintained on continuous ambulatory peritoneal dialysis. Their baseline haemoglobin levels were less than 9 g/dl. The absorption of rHuEPO via the i.p. route was limited. The serum erythropoietin (EPO) level was only slightly elevated from a baseline value of 27 ± 3 mU/l to a plateau of 36 ± 4 mU/l at 12-24 hours. In comparison, after s.c. injection, a peak EPO level of 81 ± 13 mU/l was obtained after 24 hours. The areas under the concentration-time curve from 0-24 hours were 803 ± 67 and 1492 ± 165 mU/l h for the i.p. and s.c. group respectively (p < 0.003). The same two groups of patients were then given rHuEPO by either the s.c. or the i.p. route over a period of 16 weeks. In the s.c. group, the haemoglobin increased significantly from 6.9 ± 0.3 g/dl to 9.8 ± 0.6 g/dl (p < 0.004). The mean rHuEPO dosage was 84 ± 9 U/kg body wt/week. In the i.p. group, despite relatively higher rHuEPO dosage (133 ± 7 U/kg body wt/week), haemoglobin levels did not increase significantly (7.0 ± 0.4 g/dl to 8.0 ± 0.4 g/dl, p = 0.09). Subcutaneous administration of rHuEPO is effective and convenient for patients maintained on continuous ambulatory peritoneal dialysis.