title: The disposition of TCNU (tauromustine) in human malignant glioma: pharmacokinetic studies and clinical implications.
abstract: Tauromustine (TCNU), 130 mg/sq m, was administered intraoperatively by nasogastric tube to 10 patients with malignant glioma (seven glioblastomas and three anaplastic astrocytomas). High-performance liquid chromatography analysis of 32 tumor specimens for TCNU revealed that tissue concentrations ranged from 0 to 554 ng/gm: TCNU was not detected in necrotic regions of the tumor. Levels of TCNU in brain adjacent to tumor were similar to those recorded within the gliomas (range 0 to 635 ng/gm). The variability in the tissue level of TCNU was partly attributable to variable absorption of the drug, since peak plasma TCNU levels ranged from 164 to 3333 ng/ml. There were close quantitative and temporal relationships between the times of peak plasma levels (median 456 ng/ml at 45 minutes after administration), peak tumor levels (median 250 ng/gm tissue at 55 minutes), and brain adjacent to tumor levels (median 256 ng/gm tissue at 50 minutes). Linear regression analysis of the ratio between tissue and plasma TCNU levels at particular times after drug administration suggest that plasma concentrations can be used to estimate tissue concentrations. This study demonstrates that TCNU enters malignant glioma. In view of the activity of TCNU against a range of tumors, a full clinical evaluation of this new nitrosourea in malignant glioma seems justified.
authors.affiliation: Department of Clinical Neurosciences (Surgical Neurology), Western General Hospital, Edinburgh, Scotland.
authors.forename: I R
authors.initials: IR
authors.lastname: Whittle
authors.forename: J S
authors.initials: JS
authors.lastname: MacPherson
authors.forename: J D
authors.initials: JD
authors.lastname: Miller
authors.forename: J F
authors.initials: JF
authors.lastname: Smyth
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000097:blood / Q000493:pharmacokinetics*; D001254:Astrocytoma / Q000097:blood / Q000378:metabolism*; D001921:Brain / Q000378:metabolism; D001932:Brain Neoplasms / Q000097:blood / Q000378:metabolism*; D005260:Female; D005909:Glioblastoma / Q000097:blood / Q000378:metabolism*; D006801:Humans; D007427:Intracranial Pressure; D008297:Male; D008875:Middle Aged; D009607:Nitrosourea Compounds / Q000097:blood / Q000493:pharmacokinetics*; D013654:Taurine / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics
chemical_list: D000970:Antineoplastic Agents; D009607:Nitrosourea Compounds; D013654:Taurine; C052991:1-(2-chloroethyl)-3-(2-(dimethylaminosulfonyl)ethyl)-1-nitrosourea