Abstract
Bacterial pneumonia is a significant health issue in sheep, leading to economic losses and decreased welfare. This study investigated the pharmacokinetics/pharmacodynamics (PK/PD) of tildipirosin in healthy and respiratory-diseased sheep, with and without meloxicam co-administration, and identified the principal bacterial pathogens involved. Twenty native-breed sheep were allocated into four groups: Healthy +tildipirosin (HT), Healthy + meloxicam +tildipirosin (HTM), Diseased +tildipirosin (DT), and Diseased + meloxicam + tildipirosin (DTM) (n = 5 each). Tildipirosin (4 mg/kg, IM) was administered after rectal temperature normalization (≤ 40.0 °C), and meloxicam (0.5 mg/kg, SC) was given 24 h prior. Blood samples were collected at different time intervals post-injection and analyzed using validated high-performance liquid chromatography (HPLC). PK parameters were calculated with PK-Solver, and PK/PD indices (AUC/MIC and Cmax/MIC) were derived using MIC values from bacterial isolates. Nasal swabs from 30 diseased sheep revealed Pasteurella multocida and Mannheimia haemolytica as the major etiological agents associated with ovine pneumonia. MICs for tildipirosin were 0.125 µg/mL (P. multocida) and 0.25 µg/mL (M. haemolytica), confirming high susceptibility. In diseased sheep, systemic exposure to tildipirosin was markedly reduced (AUC₀–∞, Cmax, MRT), whereas meloxicam co-administration restored these parameters. All groups, except diseased sheep without adjunct therapy (DT), exceeded PK/PD efficacy thresholds (AUC/MIC ≥ 100; Cmax/MIC ≥ 8), with the highest indices consistently observed in meloxicam-treated animals. Respiratory disease markedly impaired tildipirosin pharmacokinetics, reducing systemic exposure and therapeutic duration. Co-administration of meloxicam improved drug disposition and restored PK/PD target attainment. These results underscore the importance of integrating pathogen profiling, MIC determination, PK/PD modeling, and adjunctive anti-inflammatory therapy to optimize antimicrobial strategies in veterinary respiratory medicine.

Key words: Tildipirosin, Meloxicam, PK/PD, Respiratory infection, Goat