Pharmacokinetics of pegylated recombinant human megakaryocyte growth and development factor in healthy volunteers and patients with hematological disorders

European Journal of Haematology
Hideji TanakaHideaki Mizoguchi

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

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Citations

Aug 13, 2009·Advanced Drug Delivery Reviews·Gianfranco Pasut, Francesco M Veronese
Apr 13, 2007·Clinical Pharmacology and Therapeutics·J A WidnessP Veng-Pedersen

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