NESP

NESP Mechanism of Action

darbepoetin alfa

Manufacturer:

Kyowa Kirin

Distributor:

DCH Auriga - Healthcare
/
Four Star
Full Prescribing Info
Action
Pharmacology: NESP exerts an erythropoietic effect by acting on erythroid progenitor cells directly.
Erythropoietic Action: When intravenously administered to healthy rats and mice, NESP showed an erythropoietic effect (increasing the hemoglobin concentration and the reticulocyte count) more sustained than that of epoetin alfa. Moreover, when intravenously or subcutaneously administered to rats with renal anemia, NESP brought about a marked improvement in anemia. In partially nephrectomized rats, NESP showed an effect of improving anemia equivalent to that of epoetin alfa in a lower administration frequency.
Mechanism of Action: By binding with erythropoietin receptors, NESP acted on human hematopoietic progenitor cells to promote colony formation of late erythroid progenitor cells (CFU-E) and early erythroid progenitor cells (BFU-E) in a concentration-dependent manner (in vitro).
Clinical Studies: Double-blind comparative studies (in patients receiving hemodialysis): NESP or epoetin alfa was intravenously administered to 121 patients with renal anemia receiving hemodialysis (61 patients treated with NESP, 60 patients treated with epoetin alfa) for 28 weeks to examine the equivalence. As a result, once weekly administration of NESP proved to be equivalent to 2-3 times weekly administration of epoetin alfa in efficacy. (See Figure 1.)

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Long-term administration studies (in patients receiving hemodialysis): NESP was intravenously administered to 513 patients with renal anemia receiving hemodialysis at a dose adjusted appropriately in the range of 10-120 μg in a frequency of once weekly or once every two weeks for a long-term period. As a result, the hemoglobin concentration remained at around 11.0 g/dL during the treatment in both of the frequencies. (See Figure 2.)

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Comparability studies (in patients with chronic kidney disease not on dialysis): NESP or epoetin alfa was subcutaneously administered to 100 renal anemia patients with chronic kidney disease not on dialysis (50 patients received NESP and 50 patients received epoetin alfa) for 26 - 28 weeks to evaluate comparability. As a result, once every two weeks or once every four weeks administration of NESP proved to be equivalent to once weekly or once every two weeks administration of epoetin alfa in efficacy. (See Figure 3.)

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Long-term administration studies (in patients with chronic kidney disease not on dialysis): NESP was subcutaneously administered to 161 renal anemia patients with chronic kidney disease not on dialysis in a frequency of once every two weeks or once every four weeks for 46 - 48 weeks. Dose was adjusted in 60, 90, 120 or 180 μg. As a result, after starting administration of NESP, the hemoglobin concentration increased, and after 14 weeks and thereafter the hemoglobin concentration remained at around 12.0 g/dL. (See Figure 4.)

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General clinical studies (in patients receiving peritoneal dialysis): NESP was intravenously or subcutaneously administered to 146 patients receiving peritoneal dialysis in a frequency of once every two weeks or once every four weeks for 26 - 28 weeks. Dose was adjusted in 30, 60, 90, 120 or 180 μg. As a result, after starting administration of NESP, the hemoglobin concentration increased, and after 14 weeks and thereafter the hemoglobin concentration remained at around 12.0 g/dL. (See Figure 5.)

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Pharmacokinetics: Serum concentration: Single administration: 1) Intravenous administration: Following a single intravenous administration of NESP at a dose of 10-180 μg to patients with renal anemia receiving hemodialysis, the serum concentration increased almost dose proportionally and its time-course changes showed biphasic elimination. The pharmacokinetic parameters are shown below. AUC also increased almost in proportion to the dose. (See Figure 6 and Table 2.)

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2) Subcutaneous administration: Following a single subcutaneous administration of NESP at a dose of 20-180 μg to patients with chronic kidney disease not on dialysis, the serum concentration increased almost dose proportionally. The pharmacokinetic parameters are shown below. AUC also increased almost in proportion to the dose. (See Figure 7 and Table 3.)

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Repeated administration: Following repeated intravenous administration of NESP at a dose of 10-60 μg to patients with renal anemia receiving hemodialysis for 28 weeks, no change was found in the pharmacokinetics at the final administration when compared to the initial administration. Following repeated intravenous administration of NESP at a dose of 10-180 μg to patients with renal anemia receiving dialysis, no major change was found in the serum trough concentration.
Following repeated subcutaneous administration of NESP at a dose of 15-180 μg to patients with peritoneal dialysis patients and patients with chronic kidney disease not on dialysis, no major change was found in the serum trough concentration.
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