title: 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.
mesh_terms: D015092:3-Deazauridine / Q000134:cerebrospinal fluid / Q000378:metabolism* / Q000494:pharmacology; D001812:Blood-Brain Barrier; D001921:Brain / Q000378:metabolism*; D001932:Brain Neoplasms / Q000134:cerebrospinal fluid / Q000188:drug therapy / Q000378:metabolism*; D006801:Humans; D008577:Meningeal Neoplasms / Q000188:drug therapy; D009132:Muscles / Q000378:metabolism; D014529:Uridine / Q000031:analogs & derivatives*
chemical_list: D015092:3-Deazauridine; D014529:Uridine