The absorption, distribution and excretion of prothidium in rats, rabbits and cattle.

2-Amino-7-(2-amino-6-methylpyrimidin-4-ylamino)-9-p-aminophenylphenanthridine 10,1'-dimethobromide (Prothidium), a prophylactic drug against cattle trypanosomiasis, was concentrated in the liver and kidneys of rats and rabbits after intraperitoneal or intracardial injection; it was detectable in these organs for 7 days in rats and 10 days in rabbits. The drug protected adult rats against Trypanosoma vivax for 8 weeks. Histological examination of the organs of rats treated with Prothidium indicated that no damage had been incurred from the treatment. When cattle were treated subcutaneously, elongated swellings appeared at the site of injection which disappeared within 6 weeks. Excretion of unchanged Prothidium occurred via the bile in rats and the drug was detectable in the bile for 9 days, but no Prothidium could be detected in the faeces or urine of rats or rabbits. No metabolic products of the Prothidium were found in the tissues or plasma of rats, rabbits, or cattle. In rat liver perfused for 6 hours with Prothidium only the unchanged drug was recovered. A depot of Prothidium was formed at the site of subcutaneous injection in cattle and this remained for at least 3 months. The prolonged prophylactic action was probably due to the formation of this depot since Prothidium injected intraperitoneally into a calf was excreted at a similar rate to that observed in rats and rabbits.