Biology Reference
In-Depth Information
Discussion and conclusions
The pharmacokinetic properties of rHuEPO have been extensively studied in
healthy volunteers and nephrology patients after both intravenous and subcu-
taneous dosing. Combining the clearance values for these two populations
enables a broader picture regarding dose-linearity to evolve. Despite the inter-
study differences, it is clear from Figure 1 that clearance of rHuEPO is dose
dependent. At doses >200 U/kg, clearance of rHuEPO is approximately con-
stant at 5 mL/hr/kg. At doses <200 U/kg, clearance increases as dose decreas-
es with a three-fold increase in clearance observed at 10 U/kg. This relation-
ship appears independent of population (healthy or with chronic renal failure)
or type of rHuEPO (epoetin alfa
versus
epoetin beta). Considering subcuta-
neous dosing, no clear patterns regarding dependence of absorption properties
(rate or extent) on dose have emerged from this literature review, and bioavail-
ability (although perhaps erroneously estimated) consistently lies between
20% and 40%. Upon multiple dosing, most of the data suggest that (at least
with intravenous dosing), clearance of rHuEPO increases (approximately 10%
Figure 1. Clearance of rHuEPO over a range of doses in adult healthy and nephrology subjects, based
on literature estimates. Values are presented as mean ± standard deviation (where available). Criteria
for inclusion were: single-dose IV bolus studies, sample collection over sufficient period to charac-
terize profile (at least 48 hour), clearance values given or calculated for individual dose level,
rHuEPO-naive subjects. All data are included in Tables 1 and 3.
