Pharmacokinetics of tildipirosin in pig tonsils

Tildipirosin (TD) is a semi-synthetic tylosin analog that has been approved for the treatment of respiratory diseases in pigs and cattle. This macrolide is rapidly absorbed and extensively distributed to the site of respiratory infection. Thus, lung, mean TD concentrations were characterized by a peak on day 1 and a slow decline until 17 days after administration. On the other hand, pigs can become asymptomatic carriers of Actinobacillus pleuropneumoniae (APP) in their tonsils for long periods. In the literature, antimicrobial treatments have been used to eradicate APP from tonsils. Thus, the goal of this study was to quantify the TD penetration in tonsils and to characterize its pharmacokinetic profile at the registered dose (4 mg of TD/Kg bw) as a first step to check the potential use of this molecule for eradication of APP from tonsils in carrier animals

Forty-eight 2-month-old clinically healthy hybrid pigs were randomly divided into six groups (control, T1, T2 (1), T2(5), T2(10) and T2(15)) of eight animals. T1 and T2 groups received a dose of 2 and 4 mg of TD/Kg bw in one shot respectively and the control group received 2 mL of saline solution. The animals were sacrificed by intravenous administration of pentobarbital sodium twenty four hours after finishing the treatment for the control, T1 and T2(1) groups whereas animals of T2(5), T2(10) and T2(15) were sacrificed at 5, 10 and 15 days, post-treatment, respectively. Tonsils and blood samples were taken at necropsy to quantify the concentration of TD using a high-performance liquid chromatography (HPLC) with tandem mass spectroscopy detection (LC/MS/MS). Plasma and tonsil PK parameters were determined with a non-compartmental analysis

Average tildipirosin plasma (ATPC) and tonsil (ATTC) concentration for the control, T1 and T2(1) group increased significantly (p< 0.05) in a dosedependent manner. On the other hand, the concentration in plasma was always significantly lower (p< 0.05) than in tonsil for the groups treated with 4 mg of TD/kg bw at 1, 5, 10 and 15 days post-treatment, while the maximum concentration of tildipirosin in tonsil was observed at 1 day post-administration with a gradual decrease until 15 days post-administration. In particular, mean tonsil tildipirosin concentration is above the MIC₉₀ (2 µg/mL) for APP for about 5 days

The data demonstrate that tildipirosin is present in tonsils above MIC₉₀ for APP for an extended period of time. Further in vivo studies with carrier pigs will need to be pursued to show that the concentrations are effectively able to eliminate APP from tonsils. The results provide a good basis to continue work in this area

Disclosure of Interest: None Declared.