Comparative pharmacokinetic disposition of closantel in sheep and goats

The pharmacokinetic disposition of closantel was examined following intraruminal (i.r.) or intramuscular (i.m.) administration to adult Merino sheep and to adult and 3-month-old, suckling Angora goats. In adult goats the maximum concentration (Cmax) and area under the plasma concentration with time curve (AUC) following 3.75, 7.5 and 15.0 mg closantel/kg given i.r. increased with dose however the time of Cmax (Tmax = 2.6d) in plasma was unaffected by dose rate. The elimination phase (K10) of closantel was monoexponential with a half-life (t1/2) of 4.7d again unaffected by dose rate. Apart from a more rapid absorption phase and earlier Tmax following 3.75 mg closantel/kg i.m., pharmacokinetic behaviour was similar to that following i.r. administration at 3.75 or 7.5 mg/kg. Although absorption rate was more rapid in kids after i.r. administration at 7.5 mg/kg, pharmacokinetic disposition of closantel was otherwise similar to that in adult goats. No closantel was detected in milk of treated doses or in the plasma of their kids. I.R. closantel at 7.5 mg/kg was more slowly absorbed in goats than in sheep but Cmax was similar in both species. However, K10 t1/2 was significantly shorter in goats (4d) than in sheep (14d). Faster elimination resulted in an almost three-fold lowering of AUC in goats and could dramatically reduce the sustained action of closantel in this species compared with sheep.