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Vet J. 2014 Jul;201(1):109-15. doi: 10.1016/j.tvjl.2014.05.010. Epub 2014 May 13.

Integration of pharmacokinetic and pharmacodynamic indices of valnemulin in broiler chickens after a single intravenous and intramuscular administration.

Author information

1
Laboratory of Veterinary Pharmacology, College of Veterinary Medicine, South China Agricultural University, Guangzhou, 510642, China.
2
8725, John J Kingman Rd, MS 6201, Ft Belvoir, VA, 22060-6201, USA.
3
Laboratory of Veterinary Pharmacology, College of Veterinary Medicine, South China Agricultural University, Guangzhou, 510642, China. Electronic address: gale@scau.edu.cn.

Abstract

The antibacterial efficacy of valnemulin against Staphylococcus aureus was studied ex vivo in broiler chickens after intravenous and intramuscular administration at a dose of 10 mg/kg bodyweight (BW). The minimum inhibitory concentrations (MICs) of valnemulin against S. aureus strains ATCC 25923 in broth and serum were 0.12 and 1 µg/mL, respectively. The MIC50 and MIC90 of valnemulin against all susceptible S. aureus strains isolated from chickens in the test population were 0.06 and 0.12 μg/mL, respectively. Protein binding, which greatly influences the efficacy of valnemulin, was assayed by equilibrium dialysate in vitro. A high binding fraction of 86.2% was found, which seems in good agreement with the difference of bacterial susceptibility tests observed in broth and serum. The surrogate index of AUC0-24/MIC required for the lowest bacteriostatic effect, and 2 log10CFU reduction in bacterial count were 24.4 h and 38.0 h, respectively. The required daily dose of valnemulin for a bacteriostatic activity was calculated to be 15 mg/kg BW based on the MIC90 of 0.12 µg/mL. Considering the slow disposition process of valnemulin and an AUC0-24 h value of more than 10-fold obtained from diseased animals, a suggested dose of 3 mg/kg BW is sufficient to achieve a satisfactory therapeutic efficacy in infected broilers. Due to the time-dependent antibacterial characteristics of valnemulin, the recommended daily dose should be split into two or three sub-doses to achieve the highest effectiveness while diminishing the risk of development of bacterial resistance.

KEYWORDS:

Broiler chickens; Dose regimen design; PK/PD model; Valnemulin

PMID:
24906499
DOI:
10.1016/j.tvjl.2014.05.010
[Indexed for MEDLINE]
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