Mycoplasma gallisepticum and Escherichia coli mixed infection model in broiler chickens for studying valnemulin pharmacokinetics

Abstract

A Mycoplasma gallisepticum-Escherichia coli mixed infection model was developed in broiler chickens, which was applied to pharmacokinetics of valnemulin in the present experiment. The velogenic M. gallisepticum standard strain S6 was rejuvenated to establish the animal model, and the wild E. coli strain O78 was injected as supplementary inoculum to induce chronic respiratory disease in chickens. The disease model was evaluated based on its clinical signs, histopathological examination, bacteriological assay, and serum plate agglutination test. The pharmacokinetics of valnemulin in infected chickens was determined by intramuscular (i.m.) injection and oral administration (per os, p.o.) of a single dose of 10 mg/kg body weight (BW). Plasma samples were analyzed by liquid chromatography-tandem mass spectrometry. The plasma concentration-time curve of valnemulin was analyzed using the noncompartmental method. After the i.m. administration, the mean values of Cmax , Tmax , AUClast , MRT, CLβ /F, Vz /F, and t1⁄2β , were 27.94 μg/mL, 1.57 h, 171.63 μg·h/mL, 4.51 h, 0.06 L/h/kg, 0.56 L/kg, and 6.50 h, respectively. By contrast, the corresponding values after p.o. administration were 5.93 μg/mL, 7.14 h, 47.60 μg·h/mL, 9.80 h, 0.22 L/h/kg, 3.35 L/kg, and 10.60 h. The disposition of valnemulin was retarded in infected chickens after both modes of extravascular administration as compared to the healthy controls. More attention should be given to monitoring the therapeutic efficacy and adverse effects of mixed infection because of higher required plasma drug concentration and enlarged AUC with valnemulin treatment.

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

“…The significant correlation between dose and AUC 24 (R 2 ϭ 0.9899) allows us to calculate the AUC 24 for other dosages. This phenomenon was confirmed in other research, i.e., for marbofloxacin PK in pigs within doses ranging from 4 to 16 mg/kg (26); however, our estimated PK parameters were somewhat different from those published previously for chickens infected by M. gallisepticum plus Escherichia coli (17). After i.m.…”

“…This difference may be explained by age and pathological situation. In our study, M. gallisepticum caused only respiratory system injury in 9-day-old chickens, while the injury from M. gallisepticum plus E. coli affected the whole body (lungs, liver, kidneys, heart, and others) in the adult chicken (17). These results emphasize the influence of age and physiological status on pharmacokinetics (27,28).…”

“…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).…”

Pharmacokinetic/Pharmacodynamic Profiles of Tiamulin in an Experimental Intratracheal Infection Model of Mycoplasma gallisepticum

“…The data from the present multiple dosage studies of tiamulin confirmed the conclusion that the AUC 24h /MIC was the PK/PD index of tiamulin. The values of AUC 24h /MIC for mycoplasmastasis (0 log 10 ccu equivalents reduction), activity of 1 log 10 ccu equivalents reduction, and 2 log 10 ccu equivalents reduction were 124, 205, and 327 h, respectively, which were much lower than those obtained from an in vivo study of valnemulin (28,820, 38,030, and 56,256 h, respectively) (36). One possible reason for the differences was that the concentration in serum was not that real one act on M. gallisepticum as the infection site is air sac or respiratory system, and antibiotic concentrations in air sac or lung are usually different from those in serum (14).…”

Up-Regulation of miR-130b-3p Activates the PTEN/PI3K/AKT/NF-κB Pathway to Defense against Mycoplasma gallisepticum (HS Strain) Infection of Chicken

“…On the one hand, MG can invade and cohabit with non-phagocytic host cells, such as Hela cells, chicken erythrocytes, and chicken embryo fibroblasts (CEF), and inner organs of chickens in a parasitic way for a long time [6,7]; on the other hand, the majority of surface antigens of MG are highly variable [5,8]. Despite great advances in promoting antibiotic and vaccine sensitivity, MG infection still occurs frequently in chickens of different ages, especially in the presence of co-infections, bringing great economic losses to poultry industry [9,10,11,12]. Therefore, clarification of the molecular mechanism of MG infection is urgently needed.…”