Biology Reference
In-Depth Information
dosing, that bioavailability was increased by two-fold. Geva et al. [42], how-
ever, concluded that the pharmacokinetic parameters in children (9-17 years)
were similar to those of adults. Additionally,Jabs et al. [44] reported a
decrease (45%) in half-life upon multiple dosing in children, which is similar
to that reported in adults. However, due to the wide range in values, compari-
son to literature estimates for adults is difficult and no dedicated studies com-
paring the parameters for adult and pediatric patients were found.
In summary, the pharmacokinetic properties of rHuEPO in pediatric
nephrology patients appear to be broadly similar to those of adults, although
no controlled studies were reported in the literature.
Pharmacokinetics in oncology patients
Despite the widespread use and licensure of rHuEPO in oncology patients
undergoing chemotherapy, no studies could be found in the literature detailing
the pharmacokinetics of rHuEPO in this population. It would appear that this
is an area worthy of investigation given the evidence that endogenous EPO lev-
els are increased, both in an acute and chronic sense, by chemotherapy admin-
istration [47, 48]. Additionally, given the apparent dose-dependent pharmaco-
kinetics in other populations, the pharmacokinetics of rHuEPO in patients with
cancer may be different given the higher doses that are routinely used (e.g.,
150 U/kg three times weekly or 40,000 U weekly). A challenge in this area
would be differentiating between the changing endogenous and exogenous
EPO given the cross-reactivity of endogenous EPO in the assays.
Pharmacokinetics in other populations
The pharmacokinetic properties of rHuEPO have been studied in very few
other populations. In a comparison between patients with liver cirrhosis and
healthy volunteers, Jensen et al. [17] did not find any difference in the phar-
macokinetic properties of epoetin beta (intravenous, 100 U/kg). Patients with
chronic obstructive pulmonary disease had similar mean concentrations and no
significant difference in terminal half-life (5.98 ± 0.67 hours, n = 7) compared
with healthy volunteers (5.87 ± 0.35 hours, n = 6) [49]. The determination of
the pharmacokinetic properties of rHuEPO in patients with myelodysplastic
←
Values given as mean (SD) [range] unless otherwise indicated. Bioavailability (F) given for cross-
over studies unless otherwise indicated. CAPD, continuous peritoneal dialysis; CL, clearance; F,
bioavailability; IP, intraperitoneal; IV, intravenous; NA, not available; SC, subcutaneous.
a
F
IP
calculated relative to SC.
b
calculated based on Ka (ln2/K
a
).
c
relative clearance (CL/F).
d
F cal-
culated for n = 2 only.
e
mean values calculated from individual values presented.
f
calculated from C
(L/hr) by *(1000/BW) where BW 38.8 and 58.6 kg.
g
recalculated from CL (mL/min/kg) by *60.
h
F
CAPD
calculated relative to predialysis value from mean [CL
predial
/CL
CAPD
]*100.
i
represents 45%
decrease from mean 8.2 hr for n = 3.
j
estimated from 4 timepoints over 24 hours only.
