Pharmacokinetics of tildipirosin in beagle dogs

Abstract

The objective of this study was to investigate the pharmacokinetic profile of tildipirosin (TD) in 24 beagle dogs following intravenous (i.v.) and intramuscular (i.m.) administration, respectively, at 2, 4, and 6 mg/kg. Plasma samples at certain time points (0-14 days) were collected, and the concentrations of drug were quantified by UPLC-MS/MS. Plasma concentration-time data and relevant parameters were described by noncompartmental through WinNonlin 6.4 software. After single i.m. injection at 2, 4, and 6 mg/kg body weight, mean maximum concentration (C max ) was 412.73 ± 76.01, 1,051 ± 323, and 1,061 ± 352 ng/ml, respectively. Mean time to reach C max was 0.36 ± 0.2, 0.08 ± 0.00, and 0.13 ± 0.07 hr after i.m. injection at 2, 4, and 6 mg/kg, respectively. The mean value of T 1/2λz for i.m. administration at doses of 2, 4, and 6 mg/kg was 71.39 ± 28.42, 91 .33 ± 50.02, and 96.43 ± 45.02 hr, respectively. The mean residence times were 63.81 ± 10.96, 35.83 ± 15.13, and 38.18 ± 16.77 hr for doses of 2, 4, and 6 mg/kg, respectively. These pharmacokinetic characteristics after i.m. administration indicated that TD could be rapidly distributed into tissues on account of the high lipid solubility and then released into plasma. In addition, the absolute bioavailability of 2 mg/kg after i.m. injection was 112%. No adverse effects were observed after i.v. and i.m. administration. Tildipirosin (20,

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

“…and i.v. administration, respectively, which are similar to those reported in pigs (Rose et al, 2013), dogs (Wang et al, 2018), and goats (Elazab & Badawy, 2020), but significantly lower than in cattle (Menge et al, 2012). The time to reach C max after i.m.…”

“…administration, respectively. These values are lower than those reported in pigs (Rose et al, 2013), goats (Elazab & Badawy, 2020), and cattle (Menge et al, 2012), but similar to a previous report in dogs (Wang et al, 2018). According to the AUC 0-t values, the absolute bioavailability of i.m.…”

“…The time to reach C max after i.m. administration was 0.33 hr, similar to pigs (0.38 hr; Rose et al, 2013) and goats (0.5 hr; Elazab & Badawy, 2020), shorter than that in cattle (0.69 hr; Menge et al, 2012), but significantly longer than in dogs (0.0833 hr; Wang et al, 2018) administered the same dose, which could be due to a difference in muscle vascularization between the species. The MAT of TD after i.m.…”

“…Plasma concentrations of TD were determined using a previously reported ultra-high-pressure liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method with slight modification (Wang et al, 2018). TD plasma samples were taken from to −20°C and melted in room temperature, the plasma sample (200 µl) was added with 800 μl acetonitrile for protein precipitation, and then were adequately shaken for 3 min.…”

“…Due to the extensive use of TD, the pharmacokinetic behavior of TD has been investigated in several animal species including pigs (Rose et al, 2013), cattle (Menge et al, 2012), goats (Elazab & Badawy, 2020), and dogs (Wang et al, 2018). The pharmacokinetic profile of TD is characterized by rapid absorption, long elimination half-life, and extensive distribution into tissues, in which the concentrations are multifold higher than those observed in corresponding plasma samples (Menge al., 2012;Rose et al, 2013).…”