{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2023,10,13]],"date-time":"2023-10-13T15:44:40Z","timestamp":1697211880698},"reference-count":41,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2004,9,3]],"date-time":"2004-09-03T00:00:00Z","timestamp":1094169600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["European J of Haematology"],"published-print":{"date-parts":[[2004,10]]},"abstract":"<jats:p><jats:bold>Abstract:\u2002<\/jats:bold>  <jats:italic>Objectives<\/jats:italic>:\u2002The purpose of this study is to examine the pharmacokinetics of pegylated recombinant human megakaryocyte growth and development factor (PEG\u2010rHuMGDF) in healthy volunteers with normal hematopoiesis and patients with idiopathic thrombocytopenic purpura (ITP), acute myeloid leukemia (AML), myelodysplastic syndromes (MDS), and aplastic anemia (AA). <jats:italic>Methods<\/jats:italic>:\u2002PEG\u2010rHuMGDF was intravenously administered to healthy volunteers and patients with ITP, AML, MDS, and AA. The serum concentration of PEG\u2010rHuMGDF was measured and the pharmacokinetics was investigated using non\u2010linear mixed\u2010effects modeling technique. <jats:italic>Results<\/jats:italic>:\u2002The systemic clearance (CL) and volume of distribution at steady\u2010state (<jats:italic>V<\/jats:italic><jats:sub>ss<\/jats:sub>) consistently decreased in the healthy subjects, when the dose increased. In AML patients, CL and <jats:italic>V<\/jats:italic><jats:sub>ss<\/jats:sub> decreased when the dose increased, but the change of CL was not statistically significant. In contrast, no significant dose dependency of these parameter estimates was observed in MDS patients. In AA patients there was no significant change in <jats:italic>V<\/jats:italic><jats:sub>ss<\/jats:sub> but the CL of the higher dose groups was slightly smaller than that of the lower dose groups. Relatively smaller CL and <jats:italic>V<\/jats:italic><jats:sub>ss<\/jats:sub> in ITP patients than those of healthy volunteers at the same dose were observed. <jats:italic>Conclusions<\/jats:italic>:\u2002This saturable pathway of CL may involve the receptor\u2010mediated endocytosis and degradation by megakaryocyte lineage cells and platelets. The saturable distribution space can be also explained by the receptors on hematopoietic cells. The non\u2010saturable distribution space corresponds to the value of plasma and interstitial fluid volume.<\/jats:p>","DOI":"10.1111\/j.1600-0609.2004.00288.x","type":"journal-article","created":{"date-parts":[[2004,9,3]],"date-time":"2004-09-03T09:26:19Z","timestamp":1094203579000},"page":"269-279","source":"Crossref","is-referenced-by-count":4,"title":["Pharmacokinetics of pegylated recombinant human megakaryocyte growth and development factor in healthy volunteers and patients with hematological 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