The pharmacodynamics of the flukicidal salicylanilides, rafoxanide, closantel and oxyclosanide

The pharmacokinetics of oxyclosanide, rafoxanide and closantel were investigated in sheep (n = 5). All three drugs were extensively (greater than 99%) bound to plasma proteins and the plasma concentration/time curve was best described by a tri-exponential equation. Closantel and rafoxanide had long terminal half-lives (mean 14.5 and 16.6 days, respectively) compared with oxyclosanide (mean 6.4 days). In a study of the efficacy of rafoxanide against Fasciola hepatica, a dose rate of 7.5 mg kg-1 against 6-week-old flukes appeared to be similarly effective to a dose rate of 2.5 mg kg-1 against 10-week-old flukes (86% and 88% efficacy, respectively), as assessed at autopsies carried out on all sheep when the flukes were 14 weeks old. Part of this putative efficacy against immature flukes may be due to rafoxanide persisting in the plasma and affecting the mature flukes when they reach the bile ducts.