Pharmacokinetics and bioavailability of tildipirosin in rabbits following single‐dose intravenous and intramuscular administration

Abstract

The objective of this study was to determine the pharmacokinetics of tildipirosin in rabbits after a single intravenous (i.v.) and intramuscular (i.m.) injection at a dose of 4 mg/kg. Twelve white New Zealand rabbits were assigned to a randomized, parallel trial design. Blood samples were collected prior to administration and up to 14 days postadministration. Plasma concentrations of tildipirosin were quantified using a validated ultra‐high‐performance liquid chromatography tandem mass spectrometry (UPLC‐MS/MS) method. The pharmacokinetic parameters were calculated using a noncompartmental model in WinNonlin 5.2 software. Following i.v. and i.m. administration, the elimination half‐life (T1/2λ) was 81.17 ± 9.28 and 96.68 ± 15.37 hr, respectively, and the mean residence time (MRTlast) was 65.44 ± 10.89 and 67.06 ± 10.49 hr, respectively. After i.v. injection, the plasma clearance rate (Cl) and volume of distribution at steady state (Vdss) were 0.28 ± 0.10 L kg‐1 h−1 and 17.78 ± 5.15 L/kg, respectively. The maximum plasma concentration (Cmax) and time to reach maximum plasma concentration (Tmax) after i.m. administration were 836.2 ± 117.9 ng/ml and 0.33 ± 0.17 hr, respectively. The absolute bioavailability of i.m. administration was 105.4%. Tildipirosin shows favorable pharmacokinetic characteristics in rabbits, with fast absorption, extensive distribution, and high bioavailability. These findings suggest that tildipirosin might be a potential drug for the prevention and treatment of respiratory diseases in rabbits.

Pharmacokinetics of Tildipirosin in Ewes after Intravenous, Intramuscular and Subcutaneous Administration

“…Following a single IV injection of tildipirosin to ewes, the apparent volume of distribution was high (5.36 ± 0.57 L/kg), indicating a wide distribution in the body, which can be attributed to a significant fraction of tildipirosin inside the cells or ion-trapping tissues. This value is lower than those reported in pigs, rabbits, cattle, and dogs [8,13,14,23], perhaps due to the analytical technique used in the present study. Nevertheless, all data exceeds 0.6 L/kg, which is the volume corresponding to the body extracellular fluid.…”

“…Tildipirosin showed acceptable absolute bioavailabilities following IM and SC administration (79.1% and 68.7%, respectively). Furthermore, high values for absolute bioavailability have been reported in rabbits, pigs, and dogs [8,13,14].…”

“…The pharmacokinetics of tildipirosin have been reported in pigs [7], cattle [8], mice [12], rabbits [13], and dogs [14]. In these studies, tildipirosin showed long half-lives and high bioavailabilities after extravascular administration.…”

Pharmacokinetics of Tildipirosin in Healthy and Mycoplasma gallisepticum Infected Chickens

“…Tildipirosin, a semisynthetic macrolide antibiotic, has been marketed solely for veterinary use and is predominantly employed for management of respiratory diseases in bovine and pigs induced by multiple pathogens including Actinobacillus pleuropneumoniae, Mannhemia haemolytica, Pasteurella multocida, Haemophilus parasuis (EMA 2010;Torres et al 2016). It is distinguished by its prolonged action after a single-dose injection regimen which subsequently reduce stress from frequent animal handling (Xiong et al 2020). Tildipirosin's bacteriostatic effect is owed to its blocking action on the 50S ribosomal subunit of bacteria, hence hindering the protein production (Schlünzen et al 2001).…”

“…The pharmacokinetics of tildipirosin have been explored in rabbits (Xiong et al 2020), pigs (Rose et al 2013), ewes (Galecio et al 2020), goats (Elazab and Badawy 2020), dog (Wang et al 2018), and cattle (Menge et al 2012). Rapid absorption, massive distribution in to tissues, and prolonged elimination half-life are the prominent characteristics of tildipirosin in the aforementioned animal species.…”