Pharmacokinetics and effects of recombinant human erythropoietin after intravenous and subcutaneous injections in healthy volunteers

Abstract

A double-blind, placebo-controlled study of the pharmacokinetics and safety of multiple doses of recombinant human erythropoietin [rHuEPO 150 or 300 U/kg either by intravenous (IV) bolus or subcutaneously (SC)] in normal male subjects demonstrated that rHuEPO had a dose- related effect on the hematocrit independent of the route of administration and that multiple doses of rHuEPO had no direct pressor effects. When rHuEPO was injected IV, a monoexponential decrease in serum EPO level was evident for 18 to 24 hours postdose. Absorption of SC injected rHuEPO occurred more slowly, with relatively low serum EPO levels being maintained for 48 hours. All rHuEPO antibody titer determinations were negative. With the exception of significant increases in hemoglobin and hematocrit, no clinically significant changes occurred. No hypertensive, convulsive, or thrombotic events were observed. Of the adverse experiences observed in 10 subjects, none was considered clinically significant, and none of the subjects dropped out because of adverse experiences.

Diagnosis and treatment of cancer‐related anemia

“…It is important to note that although newer targeted therapies such as sunitinib, erlotinib, or trastuzumab commonly contribute to anemia, the ESA package labels do not mention whether these are included under the definition of myelosuppressive agents . When dosing ESA therapy, we prefer subcutaneous (SQ) over the IV route, because doses given IV are cleared from the plasma more quickly and are therefore less effective . In our practice, we routinely use epoetin or darbepoetin extended interval dosing, such as every other week or every 3 weeks to coincide with patients' chemotherapy regimens (Table ).…”

2004 Japanese Society for Dialysis Therapy Guidelines for Renal Anemia in Chronic Hemodialysis Patients*

“…The disadvantages of subcutaneous injection include a low rate of bioavailability (approximately 20% of that for intravenous injection), a sebum thickness‐related dispersion in the absorption rate, and topical pain at the injection site. The pharmacokinetic characteristic of subcutaneous injection is that the blood level of EPO remains low, at approximately 100 mU/mL, for a long duration (high time‐averaged plasma concentration), leading to anemia‐improving effects as potent as those of intravenous injection, despite a low rate of bioavailability (54).…”

The enigma of the metabolic fate of circulating erythropoietin (Epo) in view of the pharmacokinetics of the recombinant drugs rhEpo and NESP

“…), i.e. once to twice the blood plasma volume (18–25). Hence, the peak plasma Epo concentration (U L −1 ) following i.v.…”

“…administration. Peak plasma values are achieved after 10–18 h, with bioavailability being about 30% (18, 20, 22, 24, 28, 30, 31, 42–44). The mechanism which prevents most of the Epo from entering the vascular system has not been identified.…”