title: Integration of pharmacokinetic and pharmacodynamic indices of valnemulin in broiler chickens after a single intravenous and intramuscular administration.
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.
authors.affiliation: Laboratory of Veterinary Pharmacology, College of Veterinary Medicine, South China Agricultural University, Guangzhou, 510642, China.
authors.forename: Dong-Hao
authors.initials: DH
authors.lastname: Zhao
authors.affiliation: Laboratory of Veterinary Pharmacology, College of Veterinary Medicine, South China Agricultural University, Guangzhou, 510642, China.
authors.forename: Yu-Feng
authors.initials: YF
authors.lastname: Zhou
authors.affiliation: Laboratory of Veterinary Pharmacology, College of Veterinary Medicine, South China Agricultural University, Guangzhou, 510642, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Yu
authors.affiliation: Laboratory of Veterinary Pharmacology, College of Veterinary Medicine, South China Agricultural University, Guangzhou, 510642, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Shi
authors.affiliation: Laboratory of Veterinary Pharmacology, College of Veterinary Medicine, South China Agricultural University, Guangzhou, 510642, China.
authors.forename: Xue
authors.initials: X
authors.lastname: Yang
authors.affiliation: Laboratory of Veterinary Pharmacology, College of Veterinary Medicine, South China Agricultural University, Guangzhou, 510642, China.
authors.forename: Xia
authors.initials: X
authors.lastname: Xiao
authors.affiliation: Laboratory of Veterinary Pharmacology, College of Veterinary Medicine, South China Agricultural University, Guangzhou, 510642, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Deng
authors.affiliation: 8725, John J Kingman Rd, MS 6201, Ft Belvoir, VA, 22060-6201, USA.
authors.forename: Guilin Gary
authors.initials: GG
authors.lastname: Qiao
authors.affiliation: Laboratory of Veterinary Pharmacology, College of Veterinary Medicine, South China Agricultural University, Guangzhou, 510642, China.
authors.forename: Bing-Hu
authors.initials: BH
authors.lastname: Fang
authors.affiliation: Laboratory of Veterinary Pharmacology, College of Veterinary Medicine, South China Agricultural University, Guangzhou, 510642, China. Electronic address: gale@scau.edu.cn.
authors.forename: Ya-Hong
authors.initials: YH
authors.lastname: Liu
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000900:Anti-Bacterial Agents / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology*; D019540:Area Under Curve; D002645:Chickens; D004224:Diterpenes / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology; D007273:Injections, Intramuscular / Q000662:veterinary; D008826:Microbial Sensitivity Tests / Q000662:veterinary; D011201:Poultry Diseases / Q000188:drug therapy / Q000382:microbiology; D013203:Staphylococcal Infections / Q000188:drug therapy / Q000382:microbiology / Q000662:veterinary; D013211:Staphylococcus aureus / Q000187:drug effects
chemical_list: D000900:Anti-Bacterial Agents; D004224:Diterpenes; C117845:valnemulin
keywords: Broiler chickens; Dose regimen design; PK/PD model; Valnemulin