Menge, M., Rose, M., Bohland, C., Zschiesche, E., Kilp, S., Metz, W., Allan, M., Röpke, R., Nürnberger, M. Pharmacokinetics of tildipirosin in bovine plasma, lung tissue, and bronchial fluid (from live, nonanesthetized cattle). J. vet. Pharmacol. Therap. 35, 550–559.
The pharmacokinetics of tildipirosin (Zuprevo® 180 mg/mL solution for injection for cattle), a novel 16-membered macrolide for treatment, control, and prevention of bovine respiratory disease, were investigated in studies collecting blood plasma, lung tissue, and in vivo samples of bronchial fluid (BF) from cattle. After single subcutaneous (s.c.) injection at 4 mg/kg body weight, maximum plasma concentration (Cmax) was 0.7 μg/mL. Tmax was 23 min. Mean residence time from the time of dosing to the time of last measurable concentration (MRTlast) and terminal half-life (T1/2) was 6 and 9 days, respectively. A strong dose–response relationship with no significant sex effect was shown for both Cmax and area under the plasma concentration–time curve from time 0 to the last sampling time with a quantifiable drug concentration (AUClast) over the range of doses up to 6 mg/kg. Absolute bioavailability was 78.9%. The volume of distribution based on the terminal phase (Vz) was 49.4 L/kg, and the plasma clearance was 144 mL/h/kg. The time–concentration profile of tildipirosin in BF and lung far exceeded those in blood plasma. In lung, tildipirosin concentrations reached 9.2 μg/g at 4 h, peaked at 14.8 μg/g at day 1, and slowly declined to 2.0 μg/g at day 28. In BF, the concentration of tildipirosin reached 1.5 and 3.0 μg/g at 4 and 10 h, maintained a plateau of about 3.5 μg/g between day 1 and 3, and slowly declined to 1.0 at day 21. T1/2 in lung and BF was approximately 10 and 11 days. Tildipirosin is rapidly and extensively distributed to the respiratory tract followed by slow elimination.