Pharmacokinetics of halofuginone in cattle

The pharmacokinetics of the antitheilerial drug halofuginone were evaluated in healthy calves following oral administration, at a dose of 1.2 mg/kg body weight, repeated after 48 h. The maximum plasma concentration after the first dose ranged from 3.8 to 7.7 ng/ml (6.5 ng/ml, mean) and occurred at between 12 and 32 h (22 h, mean). After the second dose, the maximum plasma concentration was 4.8-8.6 ng/ml (7.2 ng/ml, mean) occurring between 12 and 32 h (17 h, mean). The apparent terminal elimination half-life ranged from 24.2 to 28.9 h with a harmonic mean of 27.3 h. No significant difference was found in the apparent volume of distribution and the body clearance between the values calculated after the first dose and the two doses. The results show that the concentrations which persist in plasma from 8 to 120 h are above the in-vitro concentration of halofuginone required to reduce by 50% the proportion of lymphoblastoid cells containing Theileria parva schizonts (EC50 = 3 ng/ml), but the maximum plasma concentrations are only about 46% of the in-vitro optimal effective concentration, EC80 (15 ng/ml).