Antiprotozoals, triazine derivatives

Diclazuril is an anticoccidial of the benzene acetonitrile group and has an anticoccidial activity against Eimeria species. Depending on the coccidia species, diclazuril has a coccidiocidal effect on the asexual or sexual stages of the development cycle of the parasite. Treatment with diclazuril causes interruption of the coccidial cycle and of excretion of oocysts for approximately 2 to 3 weeks after administration. This allows the lambs to bridge the period of decrease of maternal immunity (observed at approximately 4 weeks of age) and calves to reduce the infection pressure of their environment.

After administration of the oral suspension, the absorption of diclazuril in lambs is poor. The maximum concentration in plasma is reached between 24 h and 48 h after dosing. The elimination half-life is about 30 hours. The metabolism of diclazuril was studied in vitro using sheep hepatocytes. Studies indicate that at 24 hours after administration, the concentration in edible tissues are far below the Acceptable Daily Intake. As a consequence, there is no need to establish Maximum Residue Limits or to determine a Withdrawal Period.

The absorption of diclazuril when administered as an oral suspension to lambs and calves is poor. In lambs, peak plasma concentrations are reached about 24 hours after dosing. The absorption decreases with the age of the lambs. The elimination half‑life is about 30 hours. In calves, kinetic profiles have been studied after administration of a single dose of 5 mg diclazuril per kg body weight and after dosing for 3 consecutive days at respectively 1 mg, 3 mg and 5 mg diclazuril per kg body weight. Following the single dose of 5 mg peak plasma concentrations in the range of 21 to 75 ng/ml were reached after 8 to 24 hours. Thereafter the concentrations decreased with an half‑life of 16 hours to concentrations below 10 ng/ml after 48 hours. Following the 3 consecutive daily doses of 1 mg diclazuril per kg body weight, mean peak plasma concentrations of 65.6 ng/ml were reached 10.5 hours after the last dose. Thereafter the concentrations decreased with a half‑life of 22 hours. The AUC0‑96 h was 2127 h.ng/ml. Comparison with the profiles obtained after the multiple doses indicated dose proportionality and linearity. The time to reach peak plasma concentrations and the subsequent depletion half‑life were independent of the dose. Following an oral dose of 5 mg diclazuril per kg body weight only low concentrations of diclazuril distribute to the edible tissues which is another indication of the poor bioavailability. In vitro studies in ovine and bovine hepatocytes indicated that the metabolic transformation of diclazuril is very limited, as was also observed for other species. In vivo studies in a number of animal species have also demonstrated that diclazuril is not excreted and excreted virtually completely unchanged with the faeces.