Effect of Carbontetrachloride-Induced Hepatopathy on the Disposition Kinetics of Closantel in Goats

Clinically healthy adult black Bengal female goats were used to investigate the pharmacokinetics of closantel following intravenous administration (10 mg/kg) both in healthy and in liver damaged goats. Induction of liver damage was done by subcutaneous injection of carbontetrachloride at 0.75 mL/kg on three occasion at 48 h interval. After administration of drug, blood samples were collected in heparinized test tubes at predetermined time. The drug concentration in plasma was measured by double beam UV– Vis spectrophotometer at 222 nm. In vitro plasma protein binding of closantel was also carried out. C_max (118.82 ± 4.85 μg/mL) and C_min (4.69 ± 0.72 μg/mL) of closantel were recorded at 0.08 and 48 h respectively after i.v. administration to healthy goats, while the above values were 144.67 ± 2.50 and 3.93 ± 0.05 μg/mL at 0.08 and 48 h respectively in liver damaged goats. The t_1/2β, Cl_B and Vd_area values were 12.92 ± 1.30 h, 0.008 ± 0.0005 L/kg/h and 0.15 ± 0.01 L/kg respectively in healthy goats, while these values were 12.84 ± 0.38 h, 0.008 ± 0.001 L/kg/h and 0.16 ± 0.005 L/kg respectively in liver damaged goats. Binding capacity and association rate constant of closantel were not altered significantly in liver damaged animal compared to healthy animal. Liver damaged condition did not alter significantly the pharmacokinetic parameters of closantel.