Abstract
The purpose of this study is to examine the pharmacokinetics of pegylated recombinant human megakaryocyte growth and development factor (PEG-rHuMGDF) in healthy volunteers with normal hematopoiesis and patients with idiopathic thrombocytopenic purpura (ITP), acute myeloid leukemia (AML), myelodysplastic syndromes (MDS), and aplastic anemia (AA). PEG-rHuMGDF was intravenously administered to healthy volunteers and patients with ITP, AML, MDS, and AA. The serum concentration of PEG-rHuMGDF was measured and the pharmacokinetics was investigated using non-linear mixed-effects modeling technique. The systemic clearance (CL) and volume of distribution at steady-state (Vss) consistently decreased in the healthy subjects, when the dose increased. In AML patients, CL and Vss 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 Vss but the CL of the higher dose groups was slightly smaller than that of the lower dose groups. Relatively smaller CL and Vss in ITP patients than those of healthy volunteers at the same dose were observed. This saturable pa...Continue Reading
References
Nov 8, 1994·Proceedings of the National Academy of Sciences of the United States of America·D J KuterR D Rosenberg
Jul 1, 1994·Cell·T D BartleyS Swift
Jun 16, 1994·Nature·F J de SauvageW J Kuang
Jun 16, 1994·Nature·S LokJ M Kramer
Jun 16, 1994·Nature·K KaushanskyF S Hagen
Jul 1, 1995·Journal of Biochemistry·T KatoE Maeda
Jun 1, 1996·British Journal of Haematology·S KosugiY Matsuzawa
Jul 1, 1996·European Journal of Haematology·S KunishimaT Naoe
Jun 1, 1996·British Journal of Haematology·T TaharaT Kato
Sep 1, 1996·Stem Cells·K UsukiA Urabe
Nov 9, 1996·Lancet·R L BasserC G Begley
Dec 1, 1996·British Journal of Haematology·J C MarshE C Gordon-Smith
Feb 6, 1997·The New England Journal of Medicine·M FanucchiL Harker
May 1, 1997·Annals of Internal Medicine·S Vadhan-RajH E Broxmeyer
Aug 15, 1997·Annals of Internal Medicine·T G MartinM A Shuman
Dec 31, 1997·British Journal of Haematology·A CeruttiC L Balduini
Feb 25, 1998·Stem Cells·M MuroneF J de Sauvage
Jun 3, 1998·British Journal of Haematology·T NagasawaT Abe
May 8, 1999·British Journal of Haematology·C S ZentA M Gewirtz
Aug 25, 1999·British Journal of Haematology·J LiD J Kuter
Mar 9, 2000·Biology of Blood and Marrow Transplantation : Journal of the American Society for Blood and Marrow Transplantation·R A NashR Champlin
Mar 30, 2001·Bone Marrow Transplantation·S N WolffJ Fay
May 4, 2001·Growth Factors·R H De BoerJ Cebon
Jul 2, 2002·Lancet·Saroj Vadhan-RajBenjamin Lichtiger
Jul 2, 2002·Blood·Shosaku NomuraYasuo Ikeda
Citations
Aug 13, 2009·Advanced Drug Delivery Reviews·Gianfranco Pasut, Francesco M Veronese
Feb 28, 2009·Journal of Clinical Pharmacology·Mahesh N SamtaniChristopher J Molloy
Apr 13, 2007·Clinical Pharmacology and Therapeutics·J A WidnessP Veng-Pedersen