[Show abstract][Hide abstract] ABSTRACT: The pharmacokinetics and mammary excretion of imidocarb dipropionate, a therapeutic/prophylactic agent against a variety of tick-borne hemoparasitic diseases in domestic animals, have been investigated in sheep and goats. A commercial formulation of imidocarb di-propionate was injected i.m. at a single dose of 3 mg/kg of body weight in 7 mature lactating ewes and 8 lactating does in good health. Blood samples were collected for 48 h after administration and milk samples were collected every 12 h for 10 d. A weak cation-exchange solid-phase procedure was used to remove imidocarb from plasma. A hexane/isoamyl alcohol liquid-liquid procedure was adopted to extract the drug from the milk of sheep. The same method was used for goat milk after exposing the matrices to enzymatic digestion. The extracted samples were analyzed by HPLC. The i.m. disposition kinetics of imidocarb in the 2 species showed significant differences in the rate of elimination (0.0075 +/- 0.002 and 0.025 +/- 0.004 L/h in sheep and goats, respectively), being faster in ewes than in does. Nevertheless, a smaller area under the concentration-time curve (12.21 +/- 0.76 and 9.49 +/- 0.54 microg/mL per h in sheep and goats, respectively), a larger volume of distribution (4.18 +/- 0.44 and 7.68 +/- 0.57 L/kg in sheep and goats, respectively), and a longer mean residence time (9.07 +/- 0.77 and 14.75 +/- 2.20 h in sheep and goats, respectively) were found in goats, suggesting a more rapid and effective drug storage in tissues during the first 48 h after the injection. The concentrations of imidocarb in milk of both species were higher than in plasma. However, a fast passage through the blood-milk barrier and a high storage of imidocarb were observed in the milk of ewes, whereas the drug concentrations were not as high nor was the extent of drug penetration from blood to milk as great in the milk of goats (AUC(milk 0-48)/AUC(plasma 0-48) = 2.5 +/- 0.45 and 1.26 +/- 0.27 in sheep and goat, respectively). Despite the differences in pharmacokinetic behavior, and considering the sensitivity of pathogens to imidocarb, the same dosage regimen can be used for clinical efficacy against Babesia spp. infection in both species. In contrast, the differences in depletion of imidocarb residue in milk and the large variability in mammary drug elimination found in goats suggests that great care should be taken in defining the withdrawal time in small ruminant dairy species.
[Show abstract][Hide abstract] ABSTRACT: In accordance with the Guidelines on Validation of Analytical Procedures suggested by the European Agency for the Evaluation of Medicinal Products (EMEA), three methods were used to assess and validate the most suitable procedure to analyse residual imidocarb concentrations in edible tissues and milk of cows, sheep and goats. Based on the criteria selected to identify the most suitable analytical method, the best performances were obtained using a hexane/isoamyl alcohol liquid-liquid extraction procedure for sheep milk; after exposing the matrices to enzymatic digestion before extraction, the same method was used for the muscle, liver, kidney and fat of sheep and goats and for goat milk; and an acetone/chloroform liquid-liquid extraction method was used for all the matrices of cows. The selected methods fulfil the validation criteria recommended by the EU authorities. The total recovery ranged from 70.1% (sheep liver) to 90.8% (cattle muscle). The accuracy of the recoveries was always <30% and the precision of the different methods was always <15% for intra-assay precision and <16% for inter-assay precision. The results obtained show that different matrices and animal species have different extraction requirements, which stresses the importance of validating routine analytical methods for appropriate combinations of species and tissues.
Italian Journal of Food Science 01/2002; 14(2):99-111. · 0.29 Impact Factor