Ethidium bromide: pharmacokinetics and efficacy against trypanosme infections in rabbits and calves

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Abstract
SUMMARY: [14C[ethidium bromide has been used to determine drug levels in tissues and body fluids of rabbits and calves following intramuscular injection. Uninfected andTrypanosoma brucei- orTrypanosoma congolense-infected animals were studied. Blood and tissue fluid levels reached a maximum within 1 h and then fell rapidly; after 96 h 80–90% of the radioactivity injected had been excreted, approximately one third in urine and two thirds in faeces. By 1 h after injection of 1 mg [14C]ethidium/kg into aT. congolense-infected calf, 70–80% of the radioactivity in blood was found to be bound to trypanosomes. Doses of 1 or 10 mg/kg were found not to be curative forT. congolenseorT. bruceiinfections in rabbits; drug treatment resulted in a period of sub-patent parasitaemia which was always followed by a relapse. Examination of the prophylactic action of ethidium in rabbits showed that the drug extended the pre-patent period following trypanosome inoculation but provided no absolute protection. A period of ‘apparent’ prophylaxis observed after drug treatment of infected rabbits has been correlated with the presence of anti-trypanosome IgG in the serum.