Epoetin beta stimulates erythropoiesis by interaction with the erythropoietin receptor on progenitor cells in the bone marrow. Methoxy polyethylene glycol-epoetin beta is a continuous erythropoietin receptor activator that shows a different activity at the receptor level characterized by a slower association to and faster dissociation from the receptor, a reduced specific activity in vitro with an increased activity in vivo, as well as an increased half-life, in contrast to erythropoietin. The average molecular mass is approximately 60 kDa of which the protein moiety plus the carbohydrate part constitutes approximately 30 kDa.
As primary growth factor for erythroid development, the natural hormone erythropoietin is produced in the kidney and released into the bloodstream in response to hypoxia. In responding to hypoxia, the natural hormone erythropoietin interacts with erythroid progenitor cells to increase red cell production.
The pharmacokinetics of methoxy polyethylene glycol-epoetin beta were studied in healthy volunteers and in anaemic patients with CKD including patients on dialysis and not on dialysis.
Following subcutaneous administration to CKD patients not on dialysis, the maximum serum concentrations of methoxy polyethylene glycol-epoetin beta were observed 95 hours (median value) after administration. The absolute bioavailability of methoxy polyethylene glycol-epoetin beta after subcutaneous administration was 54%. The observed terminal elimination half-life was 142 hours in CKD patients not on dialysis.
Following subcutaneous administration to CKD patients on dialysis, the maximum serum concentrations of methoxy polyethylene glycol-epoetin beta were observed 72 hours (median value) after administration. The absolute bioavailability of methoxy polyethylene glycol-epoetin beta after subcutaneous administration was 62% and the observed terminal elimination half-life was 139 hours in CKD patients on dialysis.
Following intravenous administration to CKD patients on dialysis, the total systemic clearance was 0.494 ml/h per kg. The elimination half-life after intravenous administration of methoxy polyethylene glycol-epoetin beta is 134 hours.
A comparison of serum concentrations of methoxy polyethylene glycol-epoetin beta measured before and after haemodialysis in 41 CKD patients showed that haemodialysis has no effect on the pharmacokinetics of this medicinal product.
An analysis in 126 CKD patients showed no pharmacokinetic difference between patients on dialysis and patients not on dialysis.
In a single dose study, after intravenous administration, the pharmacokinetics of methoxy polyethylene glycol-epoetin beta are similar in patients with severe hepatic impairment as compared to healthy subjects.
Non-clinical data show no special hazard for humans based on conventional studies of cardiovascular safety pharmacology, repeat dose toxicity and reproductive toxicity.
The carcinogenic potential of methoxy polyethylene glycol-epoetin beta has not been evaluated in long-term animal studies. It did not induce a proliferative response in non-haematological tumor cell lines in vitro. In a six-month rat toxicity study no tumorigenic or unexpected mitogenic responses were observed in non-haematological tissues. In addition, using a panel of human tissues, the in vitro binding of methoxy polyethylene glycol-epoetin beta was only observed in target cells (bone marrow progenitor cells).
No significant placental transfer of methoxy polyethylene glycol-epoetin beta was observed in the rat, and studies in animals have not shown any harmful effect on pregnancy, embryofoetal development, parturition or postnatal development. There was however a class-related reversible reduction in foetal weight and a decrease in postnatal body-weight gain of offspring at the doses causing exaggerated pharmacodynamic effects in mothers. Physical, cognitive, or sexual developments in the offspring of mothers receiving methoxy polyethylene glycol-epoetin beta during gestation and lactation were not affected. When epoetin beta was administered subcutaneously to male and female rats prior to and during mating, reproductive performance, fertility, and sperm assessment parameters were not affected.
© All content on this website, including data entry, data processing, decision support tools, "RxReasoner" logo and graphics, is the intellectual property of RxReasoner and is protected by copyright laws. Unauthorized reproduction or distribution of any part of this content without explicit written permission from RxReasoner is strictly prohibited. Any third-party content used on this site is acknowledged and utilized under fair use principles.
