Pharmacokinetics and bioavailability of valnemulin in broiler chickens

Abstract

The objective of this study was to investigate the pharmacokinetics and bioavailability of valnemulin in broiler chickens after intravenous (i.v.), intramuscular (i.m.) and oral administrations of 10 mg/kg body weight (bw). Plasma samples were analyzed by high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). Pharmacokinetic characterization was performed by non-compartmental analysis using WinNonlin program. After intravenous administration, distribution was wide with the volume of distribution based on terminal phase(V(z)) of 4.27 ± 0.99 L /kg. Mean valnemulin t(1/2β)(h), Cl(β)(L /h /kg), V(ss)(L /kg) and AUC((0-∞))(μg·h /mL) values were 2.85, 0.99, 2.72 and 10.34, respectively. After intramuscular administration, valnemulin was rapidly absorbed with a C(max) of 2.2 μg/mL achieved at 0.43 h (t(max)), and the absolute bioavailability (F) was 88.81%; and for the oral route the same parameters were 0.66 ± 0.15 μg/mL, 1.54 ± 0.27 h and 74.42%. A multiple-peak phenomenon was present after oral administration. The plasma profile of valnemulin exhibited a secondary peak during 2-6 h and a tertiary peak at 32 h. The favorable PK behavior, such as the wide distribution, slow elimination and acceptable bioavailability indicated that it is likely to be effective in chickens.

Determination of the Mutant Selection Window and Evaluation of the Killing of Mycoplasma gallisepticum by Danofloxacin, Doxycycline, Tilmicosin, Tylvalosin and Valnemulin

“…The corresponding MIC 99 and MPC levels were 0.10 and 2.40; 1.10 and 2.46 μg/mL, respectively[33–36]. While the reported pharmacokinetic measurements of tilmicosin, tylvalosin and valnemulin after oral administration at the dose of 30, 20 and 10 mg/kg showed that concentrations of these agents were far more than the MPC determined in vitro [37–39], revealing that the pharmacokinetic profile were above the MSW thoroughly. Consequently, it might be difficult for tilmicosin tylvalosin and valnemulin to select the resistance mutant.…”

In Vivo Pharmacokinetic/Pharmacodynamic Profiles of Valnemulin in an Experimental Intratracheal Mycoplasma gallisepticum Infection Model

“…Valnemulin shows excellent effectiveness for treating mycoplasmal infection and rarely induces significant resistance (16). Its PK character is also favorable; however, its chemotherapeutic properties are sparse.…”

“…Serum was obtained by centrifuging blood samples at 3,000 rpm for 10 min and freezing at Ϫ20°C immediately until analysis (within 2 weeks). The valnemulin concentrations in serum were determined via a highperformance liquid chromatography-tandem mass spectrometry (LC-MS/MS) method, as described previously (16)(17)(18). The limit of quantita- tion was confirmed to be 2.5 ng/ml (19).…”

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

“…Due to the extensive use of valnemulin, several studies on the pharmacokinetics, pharmacodynamics, distribution, and metabolism (Yang et al ., ) have been conducted in various species, including rats (Yuan et al ., ), dogs (EMA, ), broiler chickens (Wang et al ., ; Zhao et al ., ,b), Muscovy ducks (Sun et al ., ), and swine (Huang et al ., ; Zhao et al ., ,b). These results showed that valnemulin possessed favorable profiles of well absorption, wide distribution, and rapid elimination.…”