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| Content Provider | Springer Nature Link |
|---|---|
| Author | Nuthalapati, Silpa Zhou, Qingyu Guo, Ping Lv, Hua Cosenza, Stephen Reddy, M. V. Ramana Reddy, E. Premkumar Gallo, James M. |
| Copyright Year | 2012 |
| Abstract | To evaluate a mitotic inhibitor, ON01910.Na, as a potential chemotherapeutic agent for brain tumors using a series of PK/PD studies, which led to the evaluation of its structural analog, ON013105, a prodrug of the more lipophilic product, ON013100.Systemic PK characterization of ON01910 and ON013105 was completed in healthy mice. Using an orthotopic U87 glioma mouse model, brain and brain tumor distribution under steady-state conditions were evaluated for ON01910.Na and ON013105/ON013100; anticancer potential following a multiple-dose schedule of 250 mg/kg/day IP for 7 days was evaluated for ON01910.Na.ON01910 exhibited low brain and brain tumor distribution with quasi-steady-state brain/plasma (Css$_{brain}$/Css$_{plasma}$) and brain tumor/plasma (Css$_{brain tumor}$/Css$_{plasma}$) concentration ratios of 0.03 ± 0.02 and 0.14 ± 0.08, respectively. Significant antiangiogenic potential and antiproliferative capacity of ON01910 in the intracerebral model was absent. ON013100 showed high brain and brain tumor penetration with Css$_{brain}$/Css$_{plasma}$ and Css$_{brain tumor}$/Css$_{plasma}$ ratios of 0.92 ± 0.26 and 1.35 ± 0.40, respectively; its prodrug ON013105 showed negligible brain and brain tumor penetration.ON013105, not ON01910.Na, was identified as a potential anticancer drug candidate for further investigation in brain tumor chemotherapy based on the properties of ON013100. |
| Starting Page | 2499 |
| Ending Page | 2511 |
| Page Count | 13 |
| File Format | |
| ISSN | 07248741 |
| Journal | Pharmaceutical Research |
| Volume Number | 29 |
| Issue Number | 9 |
| e-ISSN | 1573904X |
| Language | English |
| Publisher | Springer US |
| Publisher Date | 2012-06-08 |
| Publisher Place | Boston |
| Access Restriction | One Nation One Subscription (ONOS) |
| Subject Keyword | Biomedical Engineering Medical Law Pharmacy Biochemistry Pharmacology/Toxicology |
| Content Type | Text |
| Resource Type | Article |
| Subject | Organic Chemistry Pharmacology Molecular Medicine Pharmacology (medical) Biotechnology Pharmaceutical Science |
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