Nitroimidazoles as modifiers of nitrosourea pharmacokinetics
Conference
·
· Int. J. Radiat. Oncol., Biol. Phys.; (United States)
OSTI ID:6264323
The effect of a number of nitroimidazole sensitizers of varying lipophilicity has been studied on the pharmacokinetics of CCNU in mice. It was found that the effectiveness of these compounds in producing pharmacokinetic effects correlated directly with their lipophilicity. The effects of MISO on the pharmacokinetics of 4 nitrosoureas of differing lipophilicity were also investigated. The plasma clearances of CCNU, BCNU and MeCCNU (high lipophilicity) were slowed by MISO whereas that of chlorozotocin (Chlz) (low lipophilicity) was unaffected. Thus, it seems that for a pharmacokinetic interaction to occur between a nitroimidazole and a nitrosourea, both the modifier and the cytotoxic agent must have a requisite degree of lipophilicity. As the same requirement appears to hold for enhancement of tumor response, these data provide further evidence that pharmacokinetic modification plays a major role in chemosensitization.
- Research Organization:
- MRC Clinical Oncology and Radiotherapeutics Unit, Cambridge, England
- OSTI ID:
- 6264323
- Report Number(s):
- CONF-8311204-
- Conference Information:
- Journal Name: Int. J. Radiat. Oncol., Biol. Phys.; (United States) Journal Volume: 10:9
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
551000 -- Physiological Systems
560152* -- Radiation Effects on Animals-- Animals
59 BASIC BIOLOGICAL SCIENCES
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
AFFINITY
ANIMALS
ANTINEOPLASTIC DRUGS
AZOLES
BIOLOGICAL EFFECTS
CHEMICAL PROPERTIES
CLEARANCE
DRUGS
HETEROCYCLIC COMPOUNDS
IMIDAZOLES
MAMMALS
MICE
MISONIDAZOLE
NITRO COMPOUNDS
NITROSO
NITROSO COMPOUNDS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
PHARMACOLOGY
RADIOSENSITIZERS
RODENTS
VERTEBRATES
560152* -- Radiation Effects on Animals-- Animals
59 BASIC BIOLOGICAL SCIENCES
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
AFFINITY
ANIMALS
ANTINEOPLASTIC DRUGS
AZOLES
BIOLOGICAL EFFECTS
CHEMICAL PROPERTIES
CLEARANCE
DRUGS
HETEROCYCLIC COMPOUNDS
IMIDAZOLES
MAMMALS
MICE
MISONIDAZOLE
NITRO COMPOUNDS
NITROSO
NITROSO COMPOUNDS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
PHARMACOLOGY
RADIOSENSITIZERS
RODENTS
VERTEBRATES