The prolonged hematologic effects of a single injection of PEG-rHuMGDF in normal and thrombocytopenic mice.

Abstract:

:A single injection of > or =10 microg/kg PEG-rHuMGDF in mice causes a dose-dependent increase in circulating platelets beginning on day 3 and peaking on days 5-6. The mean platelet volume and platelet distribution width at doses > or =100 microg/kg initially increase in a dose-dependent fashion and later decrease. However, the mean platelet volume does not change when platelets are incubated with PEG-rHuMGDF in vitro. The number of marrow megakaryocytes increases in a dose-dependent fashion as early as day 1 and peaks on day 3. Marrow megakaryocyte colony-forming units (CFU-Meg) do not increase on days 1-3 at a dose of 100 microg/kg (a dose that increases platelet numbers two- to threefold and may be clinically relevant), but the relative frequency of high ploidy megakaryocytes and the proportion of large marrow megakaryocytes (29-50 microm in diameter) increases. After a dose of 1,000 microg/kg the percentage of megakaryocytes in mitosis peaks at 24-48 hours and the percentage of megakaryocytes incorporating BrdU is maximal at 48 hours, the relatively delayed peak of BrdU incorporation most likely representing endomitosis. The relative frequency of type II and III megakaryocytes peaks on days 3 and 4, respectively. Pharmacokinetic analysis of PEG-rHuMGDF shows peak serum concentrations at 2-4 hours and a terminal half-life of 11.4+/-2.5 hours. A single injection of PEG-rHuMGDF ameliorates carboplatin-induced megakaryocytopenia and thrombocytopenia in a dose-response dependent fashion. In conclusion, a single injection of PEG-rHuMGDF increases megakaryocyte and platelet production in normal and myelo-suppressed mice.

journal_name

Exp Hematol

journal_title

Experimental hematology

authors

Ulich TR,del Castillo J,Senaldi G,Cheung E,Roskos L,Young J,Molineux G,Guo J,Schoemperlen J,Munyakazi L,Murphy-Filkins R,Tarpley JE,Toombs CF,Kaufman S,Yin S,Nelson AG,Nichol JL,Sheridan WP

doi

10.1016/s0301-472x(98)00012-5

subject

Has Abstract

pub_date

1999-01-01 00:00:00

pages

117-30

issue

1

eissn

0301-472X

issn

1873-2399

pii

S0301472X98000125

journal_volume

27

pub_type

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