Biology Reference
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Table 4. Multiple-dose pharmacokinetic parameters for intravenously (IV) administered rHuEPO in
rHuEPO-naive nephrology patients
Ref
IV Dose (U/kg)
n
No. Doses
CL
t
1/2,z
[28]
15, 50, 500
6
NA
32% decrease
7
[epoetin alfa]
3 months
NA
No further decrease
[29]
Initial: 12
11
Steady state
NA
14% decrease
(then dose-adjusted)
[epoetin alfa]
[25]
80
10
TIW
14% increase
22% decrease
[epoetin beta]
for 3 months
[31]
50, 100, 150
7
TIW for 8 wks
45% increase
40% decrease
[epoetin alfa]
[1]
Initial: 50
12
3 months
10% increase
14% decrease
(NS)
a
(Sig)
b
[9]
48-192
9
TIW
31.6% decrease
c
NA
“several weeks”
(NS)
[18]
100
12
4.1-17 months
3.2% increase
3.3%
[epoetin beta]
(NS)
decrease (NS)
[34]
3000 U
3
8 weekly doses
25% decrease
8.6% decrease
[epoetin beta]
6000 U
4
8 weekly doses
15% increase
8.6% increase
[epoetin beta]
Values calculated as % change in mean/median from single-dose estimate. CL, clearance; NA, not
available; TIW, three times a week.
a
not significantly different from single dose estimates.
b
significantly different from single dose esti-
mates.
c
single and multidose patients were different cohorts.
some investigators have reported that after an initial change (i.e., after two to
three weeks), no further changes were noted upon more long-term administra-
tion [28]. Conversely, other investigators reported no substantiative change in
pharmacokinetic properties from single-dose values after reaching a new
steady-state hemoglobin value [29] or after 56 days [34]. Jensen et al. [18],
who did not find a change in the pharmacokinetic properties (except for a
reduction in volume of distribution) of epoetin beta after long-term treatment,
hypothesized that after hemoglobin has been stabilized for a prolonged dura-
tion, the elimination rate may return towards the pretreatment value. In a num-
ber of studies, the single-dose pharmacokinetics were not assessed; however,
the authors have reported no difference upon short-term treatment and long-
term treatment. For example, Hughes et al. [27], in patients receiving intra-
venous epoetin alfa, found no difference in terminal half-life after the seventh
or ninth dose at 100 U/kg (5.1 ± 0.6 h, n = 10) and after 11 to 20 weeks of
treatment (5.6 ± 0.6 h, n = 3). Gladziwa et al. [6], again did not conduct stud-
ies in naive-patients, but concluded through literature comparison that the
