Biology Reference
In-Depth Information
Table 1. Single-dose pharmacokinetic parameters of intravenously (IV) administered rHuEPO in
healthy volunteers
Ref
IV dose (U/kg)
CL (mL/hr/kg)
t
1/2,z
(hr)
n
13.8
a,b
[11]
300 U [5 U/kg]
a
12.0 (SEM 5.3)
12
[epoetin alfa]
14.68 (3.94)
4.42 (1.18)
[14]
10
6
[epoetin beta]
50
5.38 (0.44)
5.34 (0.52)
6
[epoetin beta]
150
4.98 (0.81)
6.10 (0.88)
6
[epoetin beta]
500
3.70 (0.87)
8.49 (0.83)
6
[epoetin beta]
1000
4.08 (0.94)
11.02 (0.03)
6
[epoetin beta]
50
6
11.9 (3.1)
5 (0)
[9]
[epoetin alfa]
[15]
150
6.0 (1.0)
5.3
6
[epoetin alfa]
300
5.5 (0.6)
6.1
6
[epoetin alfa]
[7]
8.12 (1.00)
6.77 (2.71)
100
9
[epoetin alfa]
100
7.94 (1.24)
8.79 (2.19)
9
[epoetin beta]
100
6.8
c
4.92
d
[3.58-9.20]
[18]
12
[epoetin beta]
5.37
d
[3.58-9.20]
[17]
100
6.7
c
10
[epoetin beta]
Values given as mean (SD) [range] unless otherwise indicated. CL, clearance; IV, intravenous; SEM,
standard error of the mean. t
1/2,z
, terminal half-life.
a
assume mean body weight of 60 kg.
b
recalculated from mean value in L/hr by *(1000/60).
c
recalculated from median value in mL/min per 1.73 m
2
by *(60/70).
d
median.
unteers, assessments of dose-linearity are easier to determine as the drug is
being used, not as a therapeutic, but as an investigational agent. Accordingly,
more extensive sampling is done as well as testing of a greater range of doses.
Flaharty et al. [14], at doses of 10, 50, 150, 500, and 1,000 U/kg, found a trend
of decreasing clearance with increasing dose, with the most dramatic differ-
ence being between 10 and 50 U/kg (approximate three-fold decrease). The
reduction in clearance resulted in longer half-lives as dose increased, for exam-
ple from 4.42 hours at 10 U/kg to 5.30 hours at 50 U/kg and 8.50 hours at
500 U/kg. For studies conducted with single-dose groups, the results tended to
be quite variable and not always in strict agreement (Tab. 1). Over the dose
range of 100 to 150 U/kg, however, clearance was approximately 7 mL/hr/kg
and terminal half-life was approximately five hours.
