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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
 
 
 

Preclinical toxicology and safety pharmacology of brodimoprim in comparison to trimethoprim and analogs.

The toxicology and safety pharmacology of brodimoprim (Ro 10-5970), a new dihydrofolate reductase inhibitor for antimicrobial chemotherapy, are reported. The toxicity is compared to trimethoprim and other dihydrofolate reductase inhibitors of the trimethoprim type. In safety pharmacological tests brodimoprim showed no significant activity in the cardiovascular, autonomic neuroeffector or central nervous systems. Effects on urine volume and sodium and potassium excretion were not noted. The acute toxicity of brodimoprim after oral administration is low. In repeated dose studies in rats, oral doses up to 50 mg/kg/day were generally well tolerated. In the baboon no toxic effects were seen even at repeated doses up to 150 mg/kg/day; on the other hand the dog was found to be particularly sensitive to treatment as 20 mg/kg/day were poorly tolerated. Target organ systems included central nervous system, liver, red blood cell parameters and thyroid gland. Doses up to 100 mg/kg/day were not teratogenic or embryotoxic in rabbits. However, treatment with 100 mg/kg/day in reproductive toxicity studies in rats induced effects on fetal/litter weight, survival of offspring and litter size and increased the incidence of skeletal variations and malformed offspring. No mutagenicity was found in the tests performed with brodimoprim. In comparison brodimoprim shows the typical toxicity known for trimethoprim and analogs. In pyrimethamine toxic effects occurred at considerably lower doses than in the other compared compounds.[1]

References

  1. Preclinical toxicology and safety pharmacology of brodimoprim in comparison to trimethoprim and analogs. Stephan-Güldner, M. Journal of chemotherapy (Florence, Italy) (1993) [Pubmed]
 
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