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Antimicrob Agents Chemother. 2015 Jul;59(7):3754-60. doi: 10.1128/AAC.00200-15. Epub 2015 Apr 6.

In vivo pharmacokinetic/pharmacodynamic profiles of valnemulin in an experimental intratracheal Mycoplasma gallisepticum infection model.

Author information

1
College of Veterinary Medicine, National Reference Laboratory of Veterinary Drug Residues (SCAU), South China Agricultural University, Guangzhou, China.
2
Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, California, USA David Geffen School of Medicine at UCLA, Los Angeles, California, USA.
3
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.

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.

PMID:
25845865
PMCID:
PMC4468724
DOI:
10.1128/AAC.00200-15
[Indexed for MEDLINE]
Free PMC Article

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