Misonidazole toxicity and pharmacokinetics in mice: dependence on strain and size.
The toxic side-effects of misonidazole (MISO) have been studied in two strains of mice over a wide weight range. The sensitivity of the mice, determined as the LD50 within 7 days of administration, varied by almost a factor of two. Differences were seen in the same strain, with heavy mice being most sensitive, and from strain to strain, with CBA mice being more susceptible than WHT albino mice. The toxicity of the MISO was closely related to a change in the peak blood levels, but showed no correlation with biological half-life. The tissue volume available for drug distribution appears to be reduced in large, heavy mice at high drug doses, and cannot be explained simply on the basis of drug exclusion from adipose tissue. For radiobiological studies with MISO doses of more than 0.5 mg/g it is recommended that it should be administered in a dosage that will give a known blood level of the drug, rather than simply by giving a constant dose based on body weight.
D000818:Animals; D001831:Body Temperature; D001835:Body Weight; D005260:Female; D007700:Kinetics; D007928:Lethal Dose 50; D008297:Male; D051379:Mice; D008808:Mice, Inbred CBA; D008815:Mice, Inbred Strains; D008920:Misonidazole / Q000097:blood / Q000378:metabolism / Q000633:toxicity*; D013045:Species Specificity; D014018:Tissue Distribution
D008920:Misonidazole