title: In vivo pharmacokinetic/pharmacodynamic profiles of valnemulin in an experimental intratracheal Mycoplasma gallisepticum infection model.
abstract: Valnemulin, a semisynthetic pleuromutilin antibiotic derivative, is greatly active against Mycoplasma. The objective of our study was to evaluate the effectiveness of valnemulin against Mycoplasma gallisepticum in a neutropenic intratracheal model in chickens using a pharmacokinetic/pharmacodynamic (PK-PD) method. The PK of valnemulin after intramuscular (i.m.) administration at doses of 1, 10, and 20 mg/kg of body weight in M. gallisepticum-infected neutropenic chickens was evaluated by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Real-time PCR (RT-PCR) was used for quantitative detection of M. gallisepticum. The ratio of the 24-h area under the concentration-time curve divided by the MIC (AUC24/MIC) correlated well with the in vivo antibacterial effectiveness of valnemulin (R(2) = 0.9669). The AUC24/MIC ratios for mycoplasmastasis (a reduction of 0 log10 color-changing unit [CCU] equivalents/ml), a reduction of 1 log10 CCU equivalents/ml, and a reduction of 2.5 log10 CCU equivalents/ml are 28,820, 38,030, and 56,256, respectively. In addition, we demonstrated that valnemulin at a dose of 6.5 mg/kg resulted in a reduction of 2.5 log10 CCU equivalents/ml. These investigations provide a solid foundation for the usage of valnemulin in poultry with M. gallisepticum infections.
authors.affiliation: College of Veterinary Medicine, National Reference Laboratory of Veterinary Drug Residues (SCAU), South China Agricultural University, Guangzhou, China.
authors.forename: Xia
authors.initials: X
authors.lastname: Xiao
authors.affiliation: College of Veterinary Medicine, National Reference Laboratory of Veterinary Drug Residues (SCAU), South China Agricultural University, Guangzhou, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Sun
authors.affiliation: College of Veterinary Medicine, National Reference Laboratory of Veterinary Drug Residues (SCAU), South China Agricultural University, Guangzhou, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Yang
authors.affiliation: College of Veterinary Medicine, National Reference Laboratory of Veterinary Drug Residues (SCAU), South China Agricultural University, Guangzhou, China.
authors.forename: Xi
authors.initials: X
authors.lastname: Fang
authors.affiliation: College of Veterinary Medicine, National Reference Laboratory of Veterinary Drug Residues (SCAU), South China Agricultural University, Guangzhou, China.
authors.forename: Dong
authors.initials: D
authors.lastname: Wu
authors.affiliation: Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, California, USA David Geffen School of Medicine at UCLA, Los Angeles, California, USA.
authors.forename: Yan Q
authors.initials: YQ
authors.lastname: Xiong
authors.affiliation: College of Veterinary Medicine, National Reference Laboratory of Veterinary Drug Residues (SCAU), South China Agricultural University, Guangzhou, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Cheng
authors.affiliation: College of Veterinary Medicine, National Reference Laboratory of Veterinary Drug Residues (SCAU), South China Agricultural University, Guangzhou, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Chen
authors.affiliation: College of Veterinary Medicine, National Reference Laboratory of Veterinary Drug Residues (SCAU), South China Agricultural University, Guangzhou, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Shi
authors.affiliation: College of Veterinary Medicine, National Reference Laboratory of Veterinary Drug Residues (SCAU), South China Agricultural University, Guangzhou, China Jiangsu Co-Innovation Centre for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou, Jiangsu, People's Republic of China gale@scau.edu.cn.
authors.forename: Ya-Hong
authors.initials: YH
authors.lastname: Liu
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000627:therapeutic use; D002645:Chickens / Q000382:microbiology*; D004224:Diterpenes / Q000627:therapeutic use; D008826:Microbial Sensitivity Tests; D009175:Mycoplasma Infections / Q000188:drug therapy*; D045686:Mycoplasma gallisepticum / Q000187:drug effects*; D009503:Neutropenia; D011201:Poultry Diseases / Q000188:drug therapy* / Q000382:microbiology; D012141:Respiratory Tract Infections / Q000188:drug therapy; D053719:Tandem Mass Spectrometry
chemical_list: D000900:Anti-Bacterial Agents; D004224:Diterpenes; C117845:valnemulin
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