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Mycoplasma synoviae (MS) infection is a serious threat to poultry industry in China. Tilmicosin is a semisynthetic macrolide antibiotic used only in animals and has shown potential efficacy against MS, but there were no reported articles concerning the pharmacokinetics/pharmacodynamics (PK/PD) interactions of tilmicosin against MS in vitro and vivo. This study aimed to assess the antibacterial activity of tilmicosin against MS in vitro and in vivo using PK/PD model to provide maximal efficacy. The minimum inhibitory concentration (MIC) and killing rates of different drug concentrations were measured using the microdilution method in vitro. Then, tilmicosin was administered orally to the MS‐infected chickens at doses of 7.5 and 60 mg/kg, and the PK parameters of tilmicosin in joint dialysates were determined using high‐pressure liquid chromatography/tandem mass spectrometry (HPLC‐MS/MS) combined with the microdialysis technique. The antibacterial effect (△E) was calculated when the infected chickens were administered a single oral dose of tilmicosin at 4, 7.5, 15, 30, and 60 mg/kg b.w. The PK and PD data were fitted using the Sigmoid Emax model to evaluate the PK/PD interactions of tilmicosin against MS. The bactericidal activity of tilmicosin against MS was concentration dependent. Furthermore, the PK/PD index of AUC0–72h/MIC exhibited the most optimal fitting results (R2 =.98). The MS load decreased by 1, 2, and 3 Log10 CFU/mL, then AUC/MIC was determined as 13.99, 20.53, and 28.23 h, respectively, and the bactericidal effect can be achieved when the dose of MS‐infected chickens is at 31.64 mg/kg b.w. The findings of this study hold significant implications for optimizing the treatment regimen for MS infection. [ABSTRACT FROM AUTHOR]

Microdialysis is a continuous direct sampling technique used in live animals to study pharmacokinetic (PK) characteristics of drugs directly in target organs. The antibiotic tilmicosin used to treat arthritis in chickens caused by Mycoplasma synoviae. However, the PK study of tilmicosin in chicken joint has not been reported. The aim of this study was to explore the PK characteristics and penetration of tilmicosin by microdialysis incorporated with High‐Performance Liquid Chromatography Mass Spectrometry (HPLC‐MS/MS). An articular cavity microdialysis sampling model was established by determining in vivo and in vitro recovery results. Tilmicosin was orally administered to chickens and flow rate testing combined with retro‐dialysis were used to determine tilmicosin concentration in the target synovial space. HPLC‐MS/MS quantification of tilmicosin from plasma and joint dialysate indicated that recovery was negatively correlated with flow rate and the optimal perfusion rate was determined to be 1.0 μL/min. The AUC, Cmax, MRT and t1/2 in plasma were 4.6, 3.0, 2.2 and 1.6 times higher than in the joint dialysate, respectively, but Tmax did not significantly differ. The penetration of tilmicosin from plasma to joint (AUCdialysate/AUCplasma) was 0.24 and indicated tilmicosin concentration in joints was much lower than that of plasma. Microdialysis technology provides a novel technique to study pharmacokinetics directly in target tissues and our study provides a reference for the clinical use of tilmicosin for treatment of M. synoviae infections in articular cavities. [ABSTRACT FROM AUTHOR]