| Title: |
Anaemia in CKD 1-5 |
| Authors: |
Woodburn, Kathryn; Holmes, Christopher; Fong, Kei-Lai; Sloneker, Steven; Strzemienski, Paul; Solon, Eric; Ryckelynck, J.-P.; Lang, P.; Bataille, P.; Choukroun, G.; Esnault, V.; Knebelman, B.; Laville, M.; Fellous, M.; Legrand, E.; Portolés, J.; Vega, N.J.; Fernández-Fresnedo, G.; Pérez, A.; Bea, S.; Camba, M.J.; on behalf of the ATENEA Study Group; Leistikow, Frank; Heidenreich, Stephan; Cases, A.; Portoles, J.; Calls, J.; Martinez Castelao, A.; Sanchez-Guisande, D.; Espinel, E.; Carreño, Agustín; Campistol, Josep María; Arias, Manuel; Morales, Jose María; Pallardo, Luis; Franco, Antonio; Shestakova, Marina; Tsubakihara, Yoshiharu; Bessho, Masami; Suzuki, Masashi; on behalf of JH22757 Study Group; Correa-Rotter, Ricardo; Niihata, Kakuya; Tomosugi, Naohisa; Uehata, Takuya; Shoji, Tatsuya; Sonoda, Mika; Kawabata, Hiroaki; Sakaguchi, Yusuke; Suzuki, Akira; Okada, Noriyuki; Kuragano, Takahiro; Shimonaka, Yasushi; Kida, Aritoshi; Kitamura, Rie; Furuta, Minoru; Yahiro, Mana; Otaki, Yoshinaga; Nisihara, Futoshi; Nonoguchi, Hiroshi; Nakanishi, Takeshi; Mircescu, Gabriel; Stancu, Simona; Stanciu, Ana; Viasu, Liliana; Capusa, Cristina; Petrescu, Ligia; Zugravu, Adrian; Aydin, Zeki; Gursu, Meltem; Uzun, Sami; Karadag, Serhat; Tatli, Emel; Sumnu, Abdullah; Doventas, Yasemin; Koldas, Macit; Ozturk, Savas; Kazancioglu, Rumeyza; Malyszko, Yolanta; Levin-Iaina, Nomy; Malyszko, Jacek; Kozminski, Piotr; Koc-Zorawska, Ewa; Mysliwiec, Michal; Hara, Masaki; Ando, Minoru; Tsuchiya, Ken; Nitta, Kosaku; Mirescu, Gabriel; Deray, Gilbert; Garneata, Liliane; Goldsmith, David; Gorriz Teruel, Jose Luis; Martin, Pierre Yves; Mitchell, Daniell; Mori, Claudio; Schäfer, Roland; Guerin, Alain; Addison, Janet; Bridges, Ian; Di Giulio, Salvatore; Farouk, Mourad; Winearls, Chris; Kiss, Istvan; Claes, Kathleen; Galle, Jan; Costa, E.; Rocha-Pereira, P.; Sameiro-Faria, M.; Miranda, V.; Afonso, C.; Belo, L.; Marinho, C.; Bicho, M.; Santos-Silva, A.; Kim, Hyun Woo; Jang, Eun Hee; Mercadal, Lucile; Metzger, Marie; Casadevall, Nicole; Haymann, Jean-Philippe; Boffa, Jean-Jacques; Flamant, Martin; Vrtovsnik, François; Stengel, Bénédicte; Froissart, Marc; Ode, Marite; Roth, Karsten; Locatelli, Francesco; Hörl, Walter H. |
| Publisher Information: |
Oxford University Press |
| Publication Year: |
2011 |
| Collection: |
HighWire Press (Stanford University) |
| Subject Terms: |
Friday 24 June 2011 |
| Description: |
INTRODUCTION AND AIMS: Hematide™/peginesatide is a PEGylated, investigational, peptide-based erythropoiesis stimulating agent (ESA). It was designed and engineered to stimulate specifically the erythropoietin receptor (EPOr), yet it has no sequence homology to rHuEPO. Peginesatide is currently in clinical development for the treatment of anemia associated with chronic renal failure. This study was designed to determine the erythropoietic response, pharmacokinetics, tissue distribution, and major routes of elimination of 14C-peginesatide following a single intravenous (IV) dose in non-human primates. METHODS: Four male Cynomolgus monkeys were administered 2.1 mg/kg 14C-peginesatide IV and sacrificed at 48 hours for MARG analysis or at 1 or 3 weeks for QWBA analyses. Blood samples were collected at various times for pharmacokinetic and hematologic analyses. Total radioactivity in whole blood and plasma PK samples was determined by combustion/liquid scintillation counting (LSC) analyses. RESULTS: 14C-peginesatide-induced erythropoiesis was characterized by initial increases in reticulocytes and subsequent time-dependent increases in red blood cell (RBC) parameters, such as hemoglobin (Hgb). At 2 weeks, Hgb was 15.8 g/dL, a 1.9 g/dL increase over the pre-dose level. Pharmacokinetics were characterized by low clearance (0.885 and 0.520 mL/kg/h for blood and plasma, respectively) and a prolonged half-life (69.8 and 70.9 hours in blood and plasma, respectively). Radioactivity concentration was greater in plasma than blood, indicating minimal association with blood cells. QWBA C max values were generally observed at 48 hours post-dose, with the distribution likely reflecting sustained blood levels of peginesatide and confinement of test article to the vasculature with slow distribution into the tissue. At 1 week post-dose, radioactivity concentrations were decreasing in most tissues except the spleen, lymph node, bone marrow, adrenal gland (sites containing EPOr), and urine, where their increase suggested a partitioning ... |
| Document Type: |
text |
| File Description: |
text/html |
| Language: |
English |
| Relation: |
http://ckj.oxfordjournals.org/cgi/content/short/4/suppl_2/4.s2.32; http://dx.doi.org/10.1093/ndtplus/4.s2.32 |
| DOI: |
10.1093/ndtplus/4.s2.32 |
| Availability: |
http://ckj.oxfordjournals.org/cgi/content/short/4/suppl_2/4.s2.32; https://doi.org/10.1093/ndtplus/4.s2.32 |
| Rights: |
Copyright (C) 2011, European Renal Association - European Dialysis and Transplant Assoc |
| Accession Number: |
edsbas.7F323B06 |
| Database: |
BASE |