Pharmacokinetics of valnemulin after intravenous, intramuscular, and oral administration in layer chickens

Abstract

The pharmacokinetic characteristics of valnemulin in layer chickens were studied after single intravenous, intramuscular, and oral administration at a dose of 15 mg/kg body weight. Plasma samples at certain time points were collected and the drug concentrations in them by ultra high-performance liquid chromatography tandem mass spectrometry (UHPLC-MS). The concentration-time data for each individual were plotted by noncompartmental analysis for the whole three routes. Following intravenous administration, the plasma concentration showed tiny fluctuation. The elimination half-life (T1/2λz), total body clearance (Cl), and area under the plasma concentration-time curve (AUC) were 1.85 ± 0.43 h, 2.2 ± 0.9 L/h, and 7.52 ± 2.46 μg·h/mL, respectively. Following intramuscular administration, the peak concentration (C , 1.40 ± 0.43 μg/mL) was achieved at the time of 0.34 h. A multiple-peak phenomenon existed after oral administration, and the first peak and secondary peak were at 10 min and during 2-4 h, respectively, while the tertiary peak appeared during 5-15 h. The bioavailability (F %) for intramuscular and oral administration was 68.60% and 52.64%, respectively. In present study, the detailed pharmacokinetic profiles showed that this drug is widely distributed and rapidly eliminated, however has a low bioavailability, indicating that valnemulin is likely to be a favorable choice in the clinical practice.

Unraveling the Metabolic Routes of Retapamulin: Insights into Drug Development of Pleuromutilins

“…High-resolution mass spectrometry has been widely used to aid with drug discovery and development (30)(31)(32)(33). Using this technique, our research team has previously illustrated the pharmacokinetics (22) and metabolic profiles of VLM (24) and TIA (23). In the current study, the comparative metabolism of RTM in animal and human liver microsomes was investigated.…”

“…According to the European Medicines Agency (EMA), pleuromutilin incubated with hepatic cytochrome P450 (CYP) enzymes is prone to be extensively hydroxylated at the 1␤, 2␤, and 8␣ positions (21). Recently, our research team has conducted many studies on the pharmacokinetics (22) and in vitro and in vivo metabolism of VLM and TIA (23,24). However, until now, metabolic information about RTM has remained scarce.…”

Preparation, characterization, and in vivo evaluation of a polymorphic form of valnemulin hydrogen tartrate

“…Consequently, we performed pharmacokinetic studies in pigs using Form I. Various pharmacokinetic and bioavailability data for valnemulin hydrochloride have been published regarding its use in broiler chickens, rats, Muscovy ducks, layer chickens, ducks, and pigs [2223243031]. However, few studies have reported similar data for valnemulin hydrogen tartrate.…”

“…Solubility determination was performed according to the method described by Da et al [322] with some modifications. An excess amount of valnemulin hydrogen tartrate polymorphs were added to 10 mL of ultrapure water at 25°C.…”

Maximum levels of cross‐contamination for 24 antimicrobial active substances in non‐target feed. Part 8: Pleuromutilins: tiamulin and valnemulin

“…The bioavailability of valnemulin is reported to be 74.4% in fasted broiler chickens (Wang et al., 2011 ). A short communication reported a bioavailability of 52.6% in broilers with no information on the fed or fasted status (Sun et al., 2017 ). In pigs, a study suggested a bioavailability of 59% but the confidence on this value is low due to the fact that the animals receiving treatment by oral and intravenous routes were not comparable (Yuan et al., 2015 ).…”