Pharmacokinetics of diminazene aceturate (BerenilR), homidium bromide (EthidiumR) and isometamidium chloride (SamorinR) after intravenous application in Boran steers

The trypanocides BerenilR, EthidiumR and SamorinR are routinely applied intramuscularly (i.m.), however, due to the increase in drug resistance of trypanosomes, some investigators and farmers have adopted the intravenous (i.v.) route and have claimed its superiority. This study establishes the pharmacokinetics of these trypanocides after i.v. application and compares it with the pharmacokinetics after i.m. application. 14C labelled trypanocides were administered intravenously to Boran steers and the radioactivity levels were determined in plasma, tissue fluid, urine, faeces and tissues. The peak plasma levels of BerenilR and EthidiumR, after i.v. application, were approximately three to seven times higher than after i.m. application. With SamorinR they were between 18 and 36 times higher using the intravenous route. The decline of plasma levels after i.v. treatment showed two phases with all three drugs, with the level of the second phase being similar after i.v. and i.m. treatment. The tissues fluid levels were lower than the plasma levels after i.v. treatment with Berenil and Ethidium, however, they were higher than the plasma levels following the i.v. treatment with Samorin. The excretion rates were initially higher after i.v. treatment. However, the accumulated excretion was similar already ten days post treatment with Berenil and Ethidium but ten days after i.v. treatment with Samorin, two-fold higher and still approximately 50% higher sixty days post treatment. The residue level in tissue was higher after i.v. treatment. These results show that Samorin is the only drug showing higher tissue fluid than plasma levels and that after intravenous treatment higher initial peaks are achieved, which especially with Samorin increase the curative effect in areas with resistant strains. However, the high skill required to use intravenous administration for trypanosomiasis control will limit its usage. (author)