A new form of Filgrastim with sustained duration in vivo and enhanced ability to mobilize PBPC in both mice and humans.

Abstract:

:Granulocyte colony-stimulating factor (G-CSF) has proven effective in the prophylaxis of chemotherapy-induced neutropenia and as a mobilizer of peripheral blood progenitor cells. The longevity of G-CSF action is limited by its removal from the body by two mechanisms. The first is thought to be mediated via receptors (receptor mediated clearance [RMC]) predominantly on neutrophils, the second process is likely the result of renal clearance. With the intention of developing a novel form of Filgrastim (r-met HuG-CSF) with a sustained duration of action in vivo, a new derivative named SD/01 has been made by association of Filgrastim with poly(ethylene glycol). The desired properties of this new agent would include a prolonged duration of action sufficient to cover a complete single course of chemotherapy. SD/01 is shown here to sustain significantly elevated neutrophil counts in hematopoietically normal mice for 5 days. In neutropenic mice effects were noted for at least 9 days, accompanying a significant reduction in the duration of chemotherapy induced neutropenia. Normal human volunteers showed higher than baseline ANC for around 9 to 10 days after a single injection of SD/01. Data from these normal volunteers also indicate that mobilization of CD34+ cells and progenitors may occur in a more timely manner and to around the same absolute numbers as with repeated daily injections of unmodified Filgrastim. These data indicate that SD/01 represents an efficacious novel form of Filgrastim with actions sustained for between one and two weeks from a single injection.

journal_name

Exp Hematol

journal_title

Experimental hematology

authors

Molineux G,Kinstler O,Briddell B,Hartley C,McElroy P,Kerzic P,Sutherland W,Stoney G,Kern B,Fletcher FA,Cohen A,Korach E,Ulich T,McNiece I,Lockbaum P,Miller-Messana MA,Gardner S,Hunt T,Schwab G

doi

10.1016/s0301-472x(99)00112-5

keywords:

subject

Has Abstract

pub_date

1999-12-01 00:00:00

pages

1724-34

issue

12

eissn

0301-472X

issn

1873-2399

pii

S0301-472X(99)00112-5

journal_volume

27

pub_type

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