Biology Reference
In-Depth Information
cating limited extravascular distribution [1, 8, 24-26]. Three phases (tri-expo-
nential) have also been reported [27].
Single dose; dose range
Single-dose intravenous pharmacokinetic parameters in rHuEPO-naive nephro-
logy patients are summarized in Table 3. Due to the nature of treatment, few
studies investigate the pharmacokinetics of rHuEPO over a wide dose range.
Even in studies that did investigate a range of doses, it is sometimes difficult to
draw conclusions. For example, Egrie et al. [28] and Lim et al. [31] each inves-
tigated a range of doses, however, only summary pharmacokinetic parameters
across all dose groups were provided. In another study by Nielsen et al. [8], few
subjects were enrolled and it was possible that the factors of prior treatment and
different sampling durations were confounded, as those subjects who received
the low dose (50 U/kg, n = 4) had previously been receiving rHuEPO (i.e., were
non-naive) and those receiving the highest dose (150 U/kg, n = 2) were
rHuEPO-naive. Yamazaki et al. [34], using doses of 3,000 U (60 U/kg) and 600
U (120 U/kg) stated that they observed dose-dependent increases in AUC and
C
max
, however, mean clearance at the low dose was slightly higher than at the
high dose (3,000 U: 7.26 mL/hr/kg; 6,000 U: 5.84 mL/hr/kg).
Table 3. Single-dose pharmacokinetic parameters of intravenously administered rHuEPO in rHuEPO-
naive nephrology patients
Ref
IV Dose (U/kg)
CL (mL/hr/kg)
t
1/2,z
(hr)
n
[28]
15, 50, 500
NA
9.3 (3.2)
6
[epoetin alfa]
4.90 (1.7)
[29]
12
11
NA
[epoetin alfa]
[2.3-7.3]
[25]
80
6.0
a
8.75
b
19
[epoetin beta]
[5.66-17.23]
[26]
120
2.82
c
8.2
8
[epoetin beta]
[1.92-5.1]
[6.2-10.2]
[10]
300
3.1 (SEM 0.5)
11.2 (SEM 0.4)
6
[epoetin alfa]
[30]
d
8.4
b
[4.8-19]
9.4
e
100
8
[epoetin beta]
100
6.8
e
8.3
b
[6.6-13]
7
[epoetin beta]
[31]
50, 100, 150
5.69
f
7.69 (SEM 1.11)
7
[epoetin alfa]
[32]
100
6.9
f
5.6 (SEM 0.3)
12
[epoetin beta]
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