Pharmacokinetics of hypoxic cell radiosensitizers: a review. [Mice; dogs; humans]

Journal Article · · Cancer Clin. Trials; (United States)

OSTI ID:6008044

Workman, P

The comparative pharmacokinetics of various nitroimidazole radiosensitizers in different species are reviewed. Radiosensitization is dependent upon the tumor concentration at the time of radiotherapy, whereas host toxicity, including peripheral neuropathy, appears to be related to the tissue exposure or area under the curve (AUC). Nitroimidazoles penetrate lipoid membranes by passive diffusion, the rate increasing with lipophilicity. Derivatives more hydrophilic than misonidazole penetrate nervous tissues comparatively slowly. They are eliminated mainly by renal clearance. Most plasma data for intravenous radiosensitizers can be described by a two-compartment open model. But in the mouse, the kinetics of misonidazole are dose dependent with increasing apparent t1/2 and AUC at higher doses due to saturable Michaelis-Menten kinetics for metabolism.

• OSTI ID: 6008044
• Journal Information: Cancer Clin. Trials; (United States), Journal Name: Cancer Clin. Trials; (United States) Vol. 3:3; ISSN CCTRD
• Country of Publication: United States
• Language: English

Related Subjects

560152* -- Radiation Effects on Animals-- Animals
560305 -- Chemicals Metabolism & Toxicology-- Vertebrates-- (-1987)
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ANIMALS
ANOXIA
ANTINEOPLASTIC DRUGS
AZOLES
CLEARANCE
DISEASES
DISTRIBUTION
DOCUMENT TYPES
DOGS
DRUGS
EXCRETION
HETEROCYCLIC COMPOUNDS
IMIDAZOLES
KINETICS
MAMMALS
MAN
MEDICINE
MEMBRANE TRANSPORT
MICE
MISONIDAZOLE
NERVOUS SYSTEM DISEASES
NITRO COMPOUNDS
NUCLEAR MEDICINE
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
PHARMACOLOGY
PRIMATES
RADIOLOGY
RADIOSENSITIZERS
RADIOTHERAPY
RENAL CLEARANCE
REVIEWS
RODENTS
THERAPY
TISSUE DISTRIBUTION
TOXICITY
VERTEBRATES