Pharmacology of the mixed-function radio- and chemosensitizers CB 1954 and RSU 1069

Conference · Wed Aug 01 04:00:00 EDT 1984 · Int. J. Radiat. Oncol., Biol. Phys.; (United States)

OSTI ID:6407749

Workman, P; Walton, M I

The authors have studied the pharmacokinetics and metabolism in mice of CB 1954 and RSU 1069. Containing both nitro and alkylating (aziridine) substituents, these are lead compounds in the mixed-function analogue series, which show particular promise for sensitizer development. Both compounds are degraded extensively, via pathways including nitro reduction, aziridine ring hydrolysis and aziridine ring removal. RSU 1069 was eliminated more rapidly than CB 1954. Tissue/plasma ratios tended to be rather lower than those for simple nitroimidazoles of intermediate lipophilicity, which are usually close to 100%. Nevertheless, tumor concentrations were consistent with potent sensitization. There is, however, scope for pharmacokinetic fine-tuning to modify tissue penetration as appropriate.

• Research Organization: Medical Research Council Clinical Oncology and Radiotherapeutics Unit, Cambridge, England
• OSTI ID: 6407749
• Report Number(s): CONF-8311204-
• Conference Information: Journal Name: Int. J. Radiat. Oncol., Biol. Phys.; (United States) Journal Volume: 10:8
• Country of Publication: United States
• Language: English

Related Subjects

550500 -- Metabolism
560152* -- Radiation Effects on Animals-- Animals
59 BASIC BIOLOGICAL SCIENCES
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ALKYLATION
AMIDES
ANIMALS
BODY
BRAIN
CENTRAL NERVOUS SYSTEM
CHEMICAL REACTIONS
CHROMATOGRAPHY
EXPERIMENTAL NEOPLASMS
FUNCTIONS
LIQUID COLUMN CHROMATOGRAPHY
MAMMALS
MICE
NERVOUS SYSTEM
NITRO COMPOUNDS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANS
PHARMACOLOGY
RADIOSENSITIVITY EFFECTS
REDUCTION
RETENTION FUNCTIONS
RODENTS
SEPARATION PROCESSES
VERTEBRATES