Effect of dose on disposition kinetics of isometamidium chloride/hydrochloride in trypanosomiasis induced calves

Effect of dose on disposition kinetics of isometamidium (ISMM) in Indian buffalo calves was studied in view of limited applications of the drug in India. Buffalo calves were pre grouped and trypanosomiasis was induced using Trypanosoma evansi. ISMM was administered intravenously at 0.25, 0.5 and 1 mg/kg (body weight) to the grouped animals. Blood samples were collected at 0.08, 0.16, 0.33, 0.66, 1, 2, 4, 6, 8, 12, 24 and 36 h post drug administration for disposition kinetics. ISMM chloride/hydrochloride in plasma was estimated by trial and error method using high performance liquid chromatography (HPLC). The time to reach the maximum plasma concentration (Tmax), was 0.08 h for all the doses. The maximum plasma concentration (Cmax) declined rapidly and the drug could not be detected in plasma samples collected beyond 8 h post dose of 0.25 mg/kg and 24 h post dose of the other two doses, that is, 0.5 and 1 mg/kg. The distribution rate constant (α) in groups I (0.25 mg/kg), II (0.5 mg/kg) and III (1 mg/kg) were 4.77 ± 1.54, 7.44 ± 0.55 and 6.91 ± 2.57 h -1 , respectively, while t1⁄2 β values were 2.01 ± 0.16, 3.09 ± 0.30 and 2.46 ± 0.16 h, respectively. The apparent volume of distribution like Vdarea, Vdc and VdB were 0.50 ± 0.01, 0.69 ± 0.06 and 0.03 ± 0.005 L/ kg in group I; 0.35 ± 0.02, 1.98 ± 0.02 and 0.07 ± 0.005 L/kg in group II; 0.26 ± 0.01, 3.88 ± 0.49 and 0.035 ± 0.003 L/kg in group III, respectively. The value of K12 and K21 were 1.97 ± 0.83 and 0.67 ± 0.07 h -1 in group I; 4.92 ± 0.45 and 1.60 ± 0.07 h -1 in group II; 4.12 ± 0.21 and 0.89 ± 0.39 h -1 in group III, respectively. It was concluded that ISMM follows dose independent kinetics after intravenous administration in buffalo calves.