High-performance liquid chromatographic analysis of staurosporine in vivo. Its translocation and pharmacokinetics in rats
| Autor: | L R, Gurley, K O, Umbarger, J M, Kim, E M, Bradbury, B E, Lehnert |
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| Rok vydání: | 1998 |
| Předmět: |
Male
Electronic Data Processing Erythrocytes Dose-Response Relationship Drug Blood Proteins Staurosporine Rats Inbred F344 Rats Injections Intravenous Animals Spectrophotometry Ultraviolet Tissue Distribution Enzyme Inhibitors Protein Kinase Inhibitors Chromatography High Pressure Liquid Protein Binding |
| Zdroj: | Journal of chromatography. B, Biomedical sciences and applications. 712(1-2) |
| ISSN: | 1387-2273 |
| Popis: | The protein kinase inhibitor staurosporine (Stsp) has been used extensively to study physiological functions, biochemical mechanisms, and cancer therapy. Using an HPLC assay for Stsp developed in our laboratory, we find that only 0.7% of Stsp remains in circulating blood of rats 5 min after injection. In vitro, Stsp is adsorbed to red blood cells (RBC) weakly and reversibly. In vivo, all but 1.2-2.5% of Stsp injected is adsorbed by the heart and lungs in one passage through them, indicating that the endothelium acts as a major Stsp sink. Following initial adsorption, pharmacokinetic studies demonstrated that Stsp had a half-life of 51.6 min in plasma and 75.3 min in RBC. Thus, plasma Stsp was in the cancer therapy range of 1-10 ng/ml for 2.7 h following a bolus injection. This data indicates that a bolus injection of Stsp must be followed by a continuous infusion of low Stsp concentration for several days to produce the G1 arrest in cells necessary to stop cell proliferation. |
| Databáze: | OpenAIRE |
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