Pharmacology of Intrathecal VP-16-213 in Dogs

Overview

Journal J Neurooncol

Publisher Springer

Date 1992 Jul 1

PMID 1517797

Citations 2

Authors

N Savaraj

L G Feun

K Lu

K Gray

C Wang

T L Loo

Affiliations

Soon will be listed here.

Abstract

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.

Citing Articles

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Slavc I, Schuller E, Falger J, Gunes M, Pillwein K, Czech T J Neurooncol. 2003; 64(3):239-47.

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Feasibility of intraventricular administration of etoposide in patients with metastatic brain tumours.

Fleischhack G, Reif S, Hasan C, Jaehde U, Hettmer S, Bode U Br J Cancer. 2001; 84(11):1453-9.

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