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Ribozyme pharmacokinetic screening for predicting pharmacodynamic dosing regimens.
- Source :
-
Current issues in molecular biology [Curr Issues Mol Biol] 2000 Oct; Vol. 2 (4), pp. 113-8. - Publication Year :
- 2000
-
Abstract
- A significant amount of research has been devoted to the chemical stabilization of synthetic ribozymes, in part, so that applications to systemic disease can be explored. A nuclease-stabilized synthetic hammerhead ribozyme, ANGIOZYME, has been developed which targets the mRNA encoding a vascular endothelial growth factor receptor, Flt-1. Because the stimulation of this receptor may contribute to tumor neovascularization and subsequent tumor growth and metastasis, we have explored the systemic use of ANGIOZYME to down regulate this receptor in a syngeneic model of metastatic cancer. We describe here the application of pharmacokinetic analysis to the selection of a dosing regimen for pharmacodynamic screening in this murine cancer model. These studies demonstrate that the appropriate application of pharmacokinetic analysis is necessary for the optimization of systemic pharmacodynamic studies using synthetic ribozymes.
- Subjects :
- Angiogenesis Inhibitors administration & dosage
Angiogenesis Inhibitors pharmacokinetics
Angiogenesis Inhibitors pharmacology
Animals
Base Sequence
Extracellular Matrix Proteins genetics
Female
Mice
Mice, Inbred C57BL
Myosin Heavy Chains
Neoplasms, Experimental drug therapy
Neoplasms, Experimental genetics
Nonmuscle Myosin Type IIB
RNA Stability
RNA, Catalytic administration & dosage
RNA, Catalytic genetics
Vascular Endothelial Growth Factor Receptor-1
RNA, Catalytic pharmacokinetics
RNA, Catalytic pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1467-3037
- Volume :
- 2
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Current issues in molecular biology
- Publication Type :
- Academic Journal
- Accession number :
- 11471755