Study of plasma protein binding activity of isometamidium and its impact on anthelmintic activity using trypanosoma induced calf model

Aim: The objective of present study was to determine Plasma Protein Binding (PPB) activity and its effect on clinical efficacy of isometamidium after intramuscular administration in calves. The binding of drugs to plasma proteins is an important factor in controlling the availability and distribution of drugs. In general, PPB reduces the free fraction of drug available for therapeutic activity, since only the non-protein bound drug is pharmacologically active. Materials and Methods: Six calves were used for PPB study and eighteen for clinical efficacy. Isometamidium was administered @ 0.5mg/kg intramuscularly as a single dose for PPB study. Equilibrium dialysis technique was used to determine the PPB activity. For clinical efficacy, infection with Trypanosoma was induced in calves of two groups, untreated control and experimental group. Infection was confirmed after 28 days by mice inoculation test. Isometamidium @ 0.5mg/kg was administered to experimental group. Haematoobiochemical and mice inoculation tests were performed after 7 days of drug administration (Day 35). Result: The percentage of PPB activity of isometamidium was 86.71 ± 0.59 to 93.03 ± 0.63% against the concentration 9.76 ± -1 0.84 to 4.39 ± 0.20 g ml . Higher percentage of PPB activity (>86%) suggests greater duration of safety by this drug. It was found that anthelmintic activity of isometamidium was substantially affected by higher PPB. Conclusion: It was concluded that isometamidium has greater plasma protein binding capacity which did not hamper clinical efficacy of drug.