Pharmacology and toxicology of rifamide

The acute toxicity of rifamide was investigated in mice, rats, rabbits, and dogs by different routes of administration. Intravenous LD 50 values were found to be within 315–550 mg/kg. In newborn and suckling rats, subcutaneous injection produces higher mortality than in adult animals. This fact might be due to the local irritating properties of high concentrations of rifamide, as the intravenous toxicity was found to be less in young than in adult rats. A chronic toxicity test, carried out in rats for a 6-month period by the intraperitoneal route, revealed kidney damage with daily dosages of 200 mg/kg. This dosage also produced death in some animals. Evidence of pathology was less severe in animals treated with 100 mg/kg and was absent in those given 50 mg/kg. Dogs, treated intravenously with 50 mg/kg of rifamide twice daily for 6 months did not show any sign of pathology that could be attributed to the antibiotic. A preliminary investigation in pregnant rabbits, carried out with doses which produce definite toxic effects in the adult animals, did not reveal any specific fetal toxicity of rifamide. Rifamide appeared devoid of significant pharmacologic side effects. When given intramuscularly to dogs, rifamide is found in blood serum in active form. Therepeutic concentrations persist for periods of time proportional to the size of the dose. The excretion of rifamide in urine takes place only to a limited extent. From 3–10% of an intramuscular dose is excreted within 48 hours.