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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.
AuthorsXia Xiao, Jian Sun, Tao Yang, Xi Fang, Dong Wu, Yan Q Xiong, Jie Cheng, Yi Chen, Wei Shi, Ya-Hong Liu
JournalAntimicrobial agents and chemotherapy (Antimicrob Agents Chemother) Vol. 59 Issue 7 Pg. 3754-60 (Jul 2015) ISSN: 1098-6596 [Electronic] United States
PMID25845865 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2015, American Society for Microbiology. All Rights Reserved.
Chemical References
  • Anti-Bacterial Agents
  • Diterpenes
  • valnemulin
Topics
  • Animals
  • Anti-Bacterial Agents (therapeutic use)
  • Chickens (microbiology)
  • Diterpenes (therapeutic use)
  • Microbial Sensitivity Tests
  • Mycoplasma Infections (drug therapy)
  • Mycoplasma gallisepticum (drug effects)
  • Neutropenia
  • Poultry Diseases (drug therapy, microbiology)
  • Respiratory Tract Infections (drug therapy)
  • Tandem Mass Spectrometry

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