caa a22 4500 469116625 CHVBK 20180323133126.0 cr unu---uuuuu 170328e19920701xx s 000 0 eng 10.1007/BF00172472 doi (NATIONALLICENCE)springer-10.1007/BF00172472 Pharmacology of intrathecal VP-16-213 in dogs [Elektronische Daten] [Niramol Savaraj, Lynn Feun, Katherine Lu, Kenneth Gray, C. Wang, Ti Loo] Summary: VP-16-213 is an anticancer drug that is active against a number of malignancies including small cell lung cancer, lymphoma, and leukemia which are often complicated by the development of leptomeningeal carcinomatosis. To investigate the potential usefulness of VP-16-213 for intrathecal administration, the pharmacology and toxicity of intrathecal VP-16-213 was determined. VP-16-213 at varying doses (0.01-1.0 mg · kg) was instilled intrathecally in dogs. Plasma, CSF, spinal cord, and brain tissue drug concentrations were determined by radiochemical and high performance liquid chromatography technique. Drug concentrations were strikingly higher in spinal cord tissue near the injection site compared to more distal cord sites. CSF concentration of VP-16-213 is 3-4 logs higher compared to concurrent plasma levels. Severe neurotoxicity occurred at the higher doses used. Due to limited diffusion and extremely low doses which could be used without life-threatening neurotoxicity, VP-16-213 does not appear to be a useful agent for intrathecal administration. Kluwer Academic Publishers, 1992 intrathecal nationallicence VP16 nationallicence Savaraj Niramol VA Medical Center, Miami, Florida, USA aut Feun Lynn aut Lu Katherine aut Gray Kenneth aut Wang C. aut Loo Ti aut Journal of Neuro-Oncology Kluwer Academic Publishers 13/3(1992-07-01), 211-215 0167-594X 13:3<211 1992 13 11060 https://doi.org/10.1007/BF00172472 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/BF00172472 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Savaraj Niramol VA Medical Center, Miami, Florida, USA aut NATIONALLICENCE 700 1- Feun Lynn aut NATIONALLICENCE 700 1- Lu Katherine aut NATIONALLICENCE 700 1- Gray Kenneth aut NATIONALLICENCE 700 1- Wang C. aut NATIONALLICENCE 700 1- Loo Ti aut NATIONALLICENCE 773 0- Journal of Neuro-Oncology Kluwer Academic Publishers 13/3(1992-07-01), 211-215 0167-594X 13:3<211 1992 13 11060 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer