Pharmacokinetics and mammary elimination of imidocarb in sheep and goats.

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

Atrial fibrillation in horse:difficult diagnosis for a therapeutic orphan

It is generally acknowledged that atrial fibrillation (AF) is a common pathological arrhythmia in horses There is currently a debate to ascertain whether equine AF can occur per se or whether it is the consequence of cardiac pathologies. In the fist case, reversion to normal rhythm can be successfully achieved by medical cardioversion but, in the former, conversion to sinus rhythm is less successful and recurrence of AF is more common. A new generation of cardioverter-defibrillators is now available and may offer an alternative approach to pharmacological cardioversion in animals. However quinidine sulphate remains the only real therapeutic option for AF in horses despite the serious adverse effects may be associated with the treatment. The use of flecainide proved to be of limited value whereas amiodarone has shown encouraging results. The practitioner is often hesitant in using pharmacological cardioversion, as the therapeutic choice is limited and the risk related to the treatment is quite high. An equine experimental model of chronic AF has been proposed. By applying it to integrated pharmacodynamic/pharmacokinetic (PK/PD) or physiologically based pharmacokinetic (PBPK) models it could represent the most practicable approach for targeting safe and effective drug dosage regimens to expand the therapeutic opportunities for treating AF successfully in the horse