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

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• 作者：Dong-Hao Zhao^a ; ¹ ; Yu-Feng Zhou^a ; ¹ ; Yang Yu^a ; ¹ ; Wei Shi^a ; Xue Yang^a ; Xia Xiao^a ; Hui Deng^a ; Guilin (Gary) Qiao^b ; Bing-Hu Fang^a ; Ya-Hong Liu^a ; ^{gale@scau.edu.cn" class="auth_mail}
• 关键词：Valnemulin ; PK/PD model ; Broiler chickens ; Dose regimen design
• 刊名：The Veterinary Journal
• 出版年：July 2014
• 年：2014
• 卷：201
• 期：1
• 页码：109-115
• 全文大小：440 K

文摘

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 渭g/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 AUC_0–24/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 AUC_0–24 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.