Pharmacokinetic analysis of pegylated megakaryocyte growth and development factor in humans

De Boer, RH; Roskos, LK; Cheung, E; Fox, S; Basser, RL; Marty, J; Begley, CG; Cebon, J

Author(s): De Boer, RH; Roskos, LK; Cheung, E; Fox, S; Basser, RL; Marty, J; Begley, CG; Cebon, J;
Details: Publication Year 2000,Volume 18,Issue #3,Page 215-226
Journal Title: GROWTH FACTORS
Publication Type: Journal Article
Abstract: Phase 1 studies with pegylated megakaryocyte growth and development factor (PEG-rHuMGDF), a c-Mpl ligand that stimulates megakaryopoiesis, have demonstrated that PEG-rHuMGDF is biologically active alone and causes a dose-related enhancement of platelet recovery when administered after chemotherapy. Here we report the dose-ranging pharmacokinetics of PEG-rHuMGDF. Pre-injection blood samples were drawn daily for pharmacokinetic studies on 43 patients. An ELISA, established using PEG-rHuMGDF as the standard, was able to quantitate Mpl ligand at concentrations > 0.02 ng/mL. Over the dose range 0.03 to 5.0 mug/kg/day, subcutaneous administration produced linear increases in steady-state serum levels. Maximum levels of PEG-rHuMGDF attained after 5.0 mug/kg/day were 5.88 to 10.9 ng/mL. After discontinuation of PEG-rHuMGDF, concentrations of Mpl ligand returned to baseline within 5 days. The pharmacokinetics were best described by a one-compartment model with first-order absorption, an absorption delay, and non linear clearance over the first 48 hours. The mean terminal half-life was 33.3 + 16.7 hours, and the average apparent at steady state was 27.7 + 14.0 mL/h/kg; both were independent of administered dose. The apparent clearance of PEG-rHuMGDF was not predicted by platelet count. Administration of chemotherapy and Filgrastim did not alter the pharmacokinetics of PEG-rHuMGDF.
Publisher: HARWOOD ACAD PUBL GMBH
Keywords: C-MPL LIGAND; STEM-CELL FACTOR; IN-VITRO; INDUCED THROMBOCYTOPENIA; POLYETHYLENE-GLYCOL; PLATELET PRODUCTION; PROGENITOR CELLS; ADVANCED CANCER; PEG-RHUMGDF; PHASE-I
Publisher's Version: https://doi.org/10.3109/08977190009003246
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Creation Date: 2000-01-01 12:00:00