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Clinical pharmacokinetic properties of rHuEPO: a
review
Anne C. Heatherington
Amgen Inc., One Amgen Center Drive, M/S 30E-0-A, Thousand Oaks, California 91320, USA
Introduction
As with all therapeutics, the clinical endpoints for recombinant human ery-
thropoietin (rHuEPO) are the most important considerations for usage.
Understanding the pharmacokinetics of an agent allows consideration of clin-
ical questions such as:.
• f the dose is doubled,will the blood concentration double?
• If the drug is administered long-term, will it accumulate?
•Should the dose be changed if route of administration is changed?
Should the dose be altered if the patient has liver disease?
Hence, having a mechanistic understanding of the factors that influence the
serum concentrations of a drug allows for more informed decisions when treat-
ing patients. An assumption in this argument is that a relationship between
drug serum concentration and efficacy has been established. In the case of
rHuEPO, a pharmacokinetic-pharmacodynamic relationship has indeed been
established [1] wherein hemoglobin increase is delayed in response to
increased serum rHuEPO concentrations. An additional benefit of understand-
ing the pharmacokinetic properties, and their relationship to efficacy, is the
potential ability to improve patient/physician convenience and/or efficacy by
manipulation of the dose administration schedule, route, or even the molecule.
This review focuses on clinical studies that have determined the pharmaco-
kinetic properties of rHuEPO in healthy volunteers, nephrology patients (adult
and pediatric), cancer patients, and others. For each population, the available
data were considered with the following questions in mind:
What are the average values and associated variability of the pharmacoki-
netic parameters in that population for both intravenous and subcutaneous
dosing?
Do the pharmacokinetic properties remain the same over a wide dose range,
i.e., are they dose independent?
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