Abstract
Simple SummaryPneumonia is a significant cause of death in sheep flocks. Thus, antibiotics are essential for the treatment of bacterial pneumonia to reduce morbidity and mortality, but few drugs are specifically labeled for clinical use in sheep. Many of the antimicrobial clinical prescriptions that occur in sheep are classified as extra-label use, with dosage, administration frequency, indications, and drug withdrawal times usually being extrapolated from information reported in other species. Thus, the objective of this study was to determine the disposition kinetics of tildipirosin after intravenous, intramuscular, and subcutaneous administration in sheep. Throughout the experiment, all ewes were healthy and no adverse reactions were recorded. The apparent volume of distribution was high, indicating a wide distribution in the body, which can be attributed to a significant fraction of tildipirosin inside the cells, and its expected activity against intracellular bacteria. Following intramuscular administration, tildipirosin was rapidly absorbed even to a greater extent when compared to subcutaneous administration. Most of the adsorbed tildipirosin after intramuscular and subcutaneous administrations were available in the body (>70%). In brief, the excellent tolerability of this formulation and the suitable disposition of tildipirosin in the body makes it an alternative for sheep use, in conditions where the administration of antibiotics is needed to observe desired effects with the benefits of scant manipulation of animals.A single-dose disposition kinetics for tildipirosin was evaluated in clinically healthy ewes (n = 6) after intravenous (IV), intramuscular (IM), and subcutaneous (SC) administration of a commercial formulation. Tildipirosin concentrations were determined by high-performance liquid chromatography with ultraviolet detection. Plasma concentration-time data was calculated by non-compartmental pharmacokinetic methods. The apparent volume of distribution (Vz) of tildipirosin after IV administration was 5.36 ± 0.57 L/kg suggesting a wide distribution in tissues and inside the cells. The elimination half-life (t½λz) was 17.16 ± 2.25, 23.90 ± 6.99 and 43.19 ± 5.17 h after IV, IM and SC administration, respectively. Following IM administration, tildipirosin was rapidly absorbed (tmax = 0.62 ± 0.10 h) even to a greater extent than after SC administration. Time to reach peak concentration (tmax) and peak plasma concentrations (Cmax) differed significantly, but both parameters showed a more significant variability after SC than after IM administration. Bioavailabilities after extravascular administration were high (>70%). Therefore, given general adverse reactions that were not observed in any ewe and favourable pharmacokinetics, tildipirosin could be effective in treating bacterial infections in sheep.
Highlights
Pneumonia commonly develops in sheep, often due to the combination of adverse physical and physiological stress with viral and bacterial infections
Mannheimia haemolytica, Pasteurella multocida, and Mycoplasma ovipneumoniae can be cultured from the upper respiratory tract of healthy sheep
An increase in creatin kinase (CK) was determined after the IM administration of tildipirosin, this increase was short-term (24 h)
Summary
Pneumonia commonly develops in sheep, often due to the combination of adverse physical and physiological stress with viral and bacterial infections. Mannheimia haemolytica, Pasteurella multocida, and Mycoplasma ovipneumoniae can be cultured from the upper respiratory tract of healthy sheep. These specific microorganisms are the principal causes of bacterial pneumonia in sheep when simultaneous infection occurs, enhancing their pathogenicity [1,2,3]. The administration of antibiotics with penetration to the respiratory system is essential to treat bacterial pneumonia in sheep to reduce morbidity, mortality, and economic losses [4]. Much of the antimicrobial use that occurs in sheep is classified as extra-labelled use with dosage, administration frequency, indications, and times of drug withdrawal, often being extrapolated from information calculated on other species [5,6]. The determination of tildipirosin levels in biological fluids is a prerequisite procedure for dose optimization of tildipirosin therapy through pharmacokinetics in veterinary medicine
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