Biology Reference
In-Depth Information
(n = 5), however, Cheung et al. [4] essentially found the pharmacokinetic
properties of epoetin alfa unchanged.
Other considerations
Although the International Olympic Committee has banned the use of rHuEPO
since 1989, it has been misused by athletes. (See Chapter 13 by Catlin et al.
for further information.) It would be expected that the pharmacokinetic prop-
erties of rHuEPO in athletes would be similar to those determined in healthy
subjects. In one study, the concentrations in the control group of endogenous
EPO remained at approximately 10 mU/mL indicating that regular-to-moder-
ate training did not influence endogenous EPO concentrations [21]. The same
authors also determined that serum and urinary measures of rHuEPO were
markers for abuse only if measured within seven and four days after the final
injection, respectively.
In summary, after subcutaneous dosing of rHuEPO to healthy volunteers,
the absorption rate is slow, resulting in an extended terminal half-life with
bioavailability ranging from 20% to 40%. Dose- or time-dependencies are not
apparent.
Pharmacokinetics in nephrology patients
In the nephrology population, most pharmacokinetic studies have been done in
patients with end-stage renal disease who are undergoing either peritoneal
dialysis (which may be subclassified as continuous ambulatory peritoneal dial-
ysis or continuous cycling peritoneal dialysis) or hemodialysis. As most
patients studied had not previously received rHuEPO (i.e., they were rHuEPO
naive), they were generally anemic (hematocrit <30%). Few studies have been
published for patients with chronic renal insufficiency wherein some degree of
kidney function is maintained. For intravenous dosing, blood samples were
generally collected out to 48 hours (range: 21-72 hours); for subcutaneous
dosing, sampling was sometimes extended to 96 hours [2]. As the drug in
patients is not simply an investigative tool, but also a therapy, the studies are
limited in their ability to assess dose ranges and even the impact of multiple
dosing due to the confounding impact of dose adjustments over time, as well
as other factors previously outlined.
Intravenous dosing
General
As for healthy volunteers, two phases were generally evident in the serum con-
centration-time profiles of nephrology patients [2, 13, 24, 25] and the volume
of distribution was generally similar to plasma volume (40-60 mL/kg), indi-
