| Autor: |
de Serres M; Department of International Development Support, Glaxo Wellcome Inc, Research Triangle Park, North Carolina 27709, USA., Yeager RL, Dillberger JE, Lalonde G, Gardner GH, Rubens CA, Simkins AH, Sailstad JM, McNulty MJ, Woolley JL |
| Jazyk: |
angličtina |
| Zdroj: |
Stem cells (Dayton, Ohio) [Stem Cells] 1999; Vol. 17 (6), pp. 316-26. |
| DOI: |
10.1002/stem.170316 |
| Abstrakt: |
GW395058, a potent PEGylated peptide human thrombopoietin receptor (HuTPOr) agonist in vitro, is being evaluated for the treatment of thrombocytopenia. GW395058 shares no sequence homology with TPO. In this report the pharmacokinetics and hematological effects of GW395058 in rats and monkeys are described. Doses eliciting thrombocytosis in rodents (2 or 10 microg/kg s.c.) produced insufficient plasma concentration data for pharmacokinetic parameter estimate calculations. At higher i.v. doses in rats (500, 1,000 or 2,000 microg/kg) serum t1/2 (half-life) values were >20 h, and the area under the concentration time curve increased proportionally with dose. In cynomolgus monkeys GW395058 plasma t1/2 values ranged from 37 to 68 h after s.c. or i.v. dosing, and similar values were observed in rhesus monkeys following s.c. dosing. Rat platelet counts increased following 2 (1.6-fold) or 10 microg/kg (fourfold) s.c. doses. Cynomolgus and rhesus monkey platelet counts did not change significantly at comparable s.c. doses, but did increase slightly (
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| Databáze: |
MEDLINE |
| Externí odkaz: |
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