G. Steffensen et al., COMPARATIVE CROSSOVER STUDY OF INTRAVENOUSLY AND SUBCUTANEOUSLY ADMINISTERED RECOMBINANT-HUMAN-ERYTHROPOIETIN IN HEMODIALYSIS-PATIENTS, Blood purification, 10(5-6), 1992, pp. 241-247
A comparative crossover study of intravenously (i.v.) and subcutaneous
ly (s.c.) administered recombinant human erythropoietin (r-HuEPO) was
conducted in 20 patients with end-stage renal disease on maintenance h
emodialysis. The patients were randomized into two groups. Group 1 rec
eived r-HuEPO i.v. thrice weekly and group II r-HuEPO s.c. twice weekl
y for 12 weeks, then the therapy was crossed over for another 12-week
period. The initial dose was 50 U/kg/i.v. dose and 40 U/kg/s.c. dose.
In all but 1 patient an adequate hematologic response was obtained. In
group 1 the mean hemoglobin (Hb) level increased from 4.8 (Hb0) to 6.
0 after 12 weeks (Hb12) and further to 6.5 mmol/l after 24 weeks (Hb24
) throughout the study (0.025 < p < 0.05). In group II it increased fr
om 4.6 (Hb0) to 7.1 (Hb12) to 6.9 mmol/l (Hb24) (0.01 < p < 0.025). Th
ere was a significant difference between the two groups (p < 0.05). Th
e rise in Hb in group II during the first 12 weeks of the study was ac
hieved by only half the cumulative dose of r-HuEPO (11,820 U) per kilo
gram compared to the consumption in group I (24,575 U). In the last 12
weeks of the study the requirement of r-HuEPO to maintain Hb level wa
s equal in the two groups. In group I serum erythropoietin (EPO) level
increased slowly throughout the study. In group II an increment was f
ollowed by a decrease beyond prestudy level. This happened at an eryth
ropoietic response with mean hematocrit (Hct) about 35%. In group I a
mean Hct > 35% was never reached. This might indicate the existence of
an EPO-Hct feedback mechanism. In conclusion, s.c. administration is
significantly more effective than i.v. administration as induction the
rapy, requiring only half the dose of r-HuEPO. Also it can be administ
ered twice weekly, and a start dose of 40 U/kg/dose is suggested aimin
g at a Hct not exceeding 35 %.