Penetration of 3-deazauridine into human brain, intracerebral tumor, and cerebrospinal fluid.

Abstract

The antitumor agent 3-deazauridine (DAU) was administered rapidly to four patients before surgical removal of intracerebral tumor. Tumor, adjacent brain tissue, and temporalis muscle were assayed for DAU by high-pressure liquid chromatography. DAU penetrated comparably into tumor, brain, and muscle; in one patient, tissue concentrations were higher than concurrent plasma concentrations. The active metabolite 3-deazauridine 5'-triphosphate was quantitated in one tumor sample and greatly exceeded its Ki for cytidine 5'-triphosphate synthetase. DAU was also present in autopsy brain specimens from two patients treated shortly antemortem. Cerebrospinal fluid concentrations were 22.1 and 59.0%, respectively, of concurrent plasma concentrations during continuous infusion of DAU in two patients. Cerebrospinal fluid concentration was 3.1 microgram/ml 2 hr after a 30-min infusion of 1.5 g of drug per sq m and fell to 1.9 microgram/ml at 16 hr. Thus, DAU is capable of penetrating into intracerebral tumor, brain, and cerebrospinal fluid and is worthy of investigation in the treatment of intracerebral and meningeal neoplasms.

• Authors: D J Stewart, J A Benvenuto, M Leavens, S W Hall, R S Benjamin, W Plunkett, K B McCredie, M A Burgess, T L Loo
• Journal: Cancer research (Cancer Res) Vol. 39 Issue 10 Pg. 4119-22 (Oct 1979) ISSN: 0008-5472 [Print] United States
• PMID: 476649 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• 3-Deazauridine
• Uridine

Topics

• 3-Deazauridine (cerebrospinal fluid, metabolism, pharmacology)
• Blood-Brain Barrier
• Brain (metabolism)
• Brain Neoplasms (cerebrospinal fluid, drug therapy, metabolism)
• Humans
• Meningeal Neoplasms (drug therapy)
• Muscles (metabolism)
• Uridine (analogs & derivatives)