title: Pharmacokinetics and pharmacodynamics of intravenous and subcutaneous continuous erythropoietin receptor activator (C.E.R.A.) in patients with chronic kidney disease.
abstract: Continuous Erythropoietin Receptor Activator (C.E.R.A.) is a new agent that is in development for the treatment of anemia with extended administration intervals in patients who have chronic kidney disease (CKD), both those on and those not on dialysis. This was an open-label, randomized, multicenter, two-period, crossover study in erythropoiesis-stimulating agentnaïve patients who had CKD and anemia and were receiving peritoneal dialysis. After a 1-wk run-in period, 16 patients were randomly assigned to receive a single administration of intravenous C.E.R.A. 0.4 microg/kg (n = 8) or subcutaneous C.E.R.A. 0.8 microg/kg (n = 8). Six weeks after the first administration of C.E.R.A. (4-wk assessment, 2-wk washout), the route of administration was switched so that all patients received single administrations of both intravenous C.E.R.A. 0.4 microg/kg and subcutaneous C.E.R.A. 0.8 microg/kg. C.E.R.A. had a prolonged and comparable half-life after intravenous (mean 134 h) and subcutaneous (mean 139 h) administration. Reticulocyte counts peaked at a median of 8 d after intravenous and subcutaneous administration with no difference in the time course between administration routes. This resulted in similar mean values for the area under the reticulocyte count-time curve (1191 x 10(9) and 1193 x 10(9).d per L, respectively) and the maximum absolute increase in reticulocyte counts (36 x 10(9) and 41 x 10(9)/L, respectively). C.E.R.A. has a prolonged and comparable half-life after intravenous or subcutaneous injection, suggesting that extended administration intervals may be feasible in patients with CKD.
authors: Department of Renal Medicine, King's College Hospital, London, UK. iain.macdougall@kingsch.nhs.uk
authors: Iain C
authors: IC
authors: Macdougall
authors: Richard
authors: R
authors: Robson
authors: Sylvie
authors: S
authors: Opatrna
authors: Xavier
authors: X
authors: Liogier
authors: Anne
authors: A
authors: Pannier
authors: Paul
authors: P
authors: Jordan
authors: Frank C
authors: FC
authors: Dougherty
authors: Bruno
authors: B
authors: Reigner
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000740:Anemia / Q000188:drug therapy / Q000209:etiology; D018592:Cross-Over Studies; D004921:Erythropoietin / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D005260:Female; D006461:Hemolysis; D006801:Humans; D007262:Infusions, Intravenous; D007263:Infusions, Parenteral; D007676:Kidney Failure, Chronic / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D011994:Recombinant Proteins
chemical_list: D011994:Recombinant Proteins; C508420:continuous erythropoietin receptor activator; D004921:Erythropoietin; D011092:Polyethylene Glycols