Biology Reference
In-Depth Information
rHuEPO is injected into a dry peritoneum as Krömer et al. [32] obtained a
bioavailablility estimate of 41.4% (SEM 7.2, n = 12) and Ateshkadi et al. [13]
obtained an estimate of 11.4 (6.6)% (n = 8). In a comparison study, Bargman
et al. [36] obtained a nine-fold increase in AUC after administration into a dry
peritoneum compared with that injected with dialysate. Additionally, increas-
ing the dwell time within the peritoneum is thought to increase the extent of
absorption [13, 37].
Comparison of healthy volunteers and nephrology patients
When the pharmacokinetic characteristics of rHuEPO in healthy volunteers
and nephrology patients are compared across studies, it appears that the
parameters are similar. However, in the only within-study comparison study
found, Jensen et al. [18] found considerable differences in the pharmacokinet-
ics of 100 U/kg epoetin beta after both intravenous and subcutaneous dosing
in healthy (n = 12)
versus
uremic/dialysis (n = 21) subjects. After intravene-
nous dosing, clearance was statistically significantly reduced (from approxi-
mately 6.8 to 4.3 mL/hr/kg) and terminal half-life was increased (from 4.92 to
8.31 hours) in the uremic patients compared with the healthy volunteers.
Distribution parameters did not change. After subcutaneous dosing, peak con-
centrations were significantly reduced (113
versus
153 mU/mL) and bioavail-
ability was significantly lower (23.7%
versus
38.5%) in uremic patients. The
rate of absorption, however, did not appear to differ between the two groups.
The differences were not attributed to loss in dialysate. This single comparison
would need confirmation in independent studies.
Nephrology studies in pediatric patients
The pharmacokinetic properties of rHuEPO have been determined in a num-
ber of studies in pediatric nephrology patients; Table 6 summarizes the avail-
able literature for intravenous, subcutaneous, and intraperitoneal dosing. After
intravenous administration of rHuEPO to pediatric patients, the mean terminal
half-life ranged from 5.6 to 10.9 hours with mean clearance values ranging
from 6.0 to 10.1 mL/hr/kg. After subcutaneous dosing, absorption was rate
limiting such that the mean terminal half-life ranged from 13.3 to 25.2 hours
with bioavailability estimates ranging from 34% to 40%. Braun et al. [41] con-
cluded, using 20 patients, that the pharmacokinetic data of young and older
children aged 7 to 20 years were not significantly different. For intraperitoneal
dosing, Kausz et al. [45], by comparison to literature values, concluded that
(similar to adults) injection into a dry peritoneum increases bioavailability.
Evans et al. [39] concluded that, after intravenous administration in pediatric
patients (9-16 years), clearance was increased by two-fold and terminal half-
life decreased by 30% to 86% compared with adults, and after subcutaneous
