title: 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.
authors.affiliation: College of Veterinary Medicine, National Reference Laboratory of Veterinary Drug Residues, South China Agricultural University (SCAU), Guangzhou, China.
authors.forename: X
authors.initials: X
authors.lastname: Xiao
authors.forename: D H
authors.initials: DH
authors.lastname: Zhao
authors.forename: X
authors.initials: X
authors.lastname: Yang
authors.forename: W
authors.initials: W
authors.lastname: Shi
authors.forename: H
authors.initials: H
authors.lastname: Deng
authors.forename: J
authors.initials: J
authors.lastname: Ma
authors.forename: S
authors.initials: S
authors.lastname: Zhang
authors.forename: Y H
authors.initials: YH
authors.lastname: Liu
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics / Q000627:therapeutic use; D019540:Area Under Curve; D002645:Chickens; D060085:Coinfection / Q000188:drug therapy / Q000382:microbiology / Q000662:veterinary; D004224:Diterpenes / Q000493:pharmacokinetics / Q000627:therapeutic use; D004927:Escherichia coli Infections / Q000188:drug therapy / Q000382:microbiology / Q000662:veterinary*; D006207:Half-Life; D009175:Mycoplasma Infections / Q000188:drug therapy / Q000382:microbiology / Q000662:veterinary*; D045686:Mycoplasma gallisepticum; D011201:Poultry Diseases / Q000188:drug therapy / Q000382:microbiology*
chemical_list: D000900:Anti-Bacterial Agents; D004224:Diterpenes; C117845:valnemulin