Ex vivo pharmacokinetic and pharmacodynamic analysis of valnemulin against Mycoplasma gallisepticum S6 in Mycoplasma gallisepticum and Escherichia coli co-infected chickens.
Pharmacokinetic and pharmacodynamic (PK/PD) indices against Mycoplasma gallisepticum (MG) S6 were investigated in an ex vivo PK/PD model following oral administration of valnemulin to chickens co-infected with M. gallisepticum and Escherichia coli. The minimum inhibitory concentrations (MICs) for valnemulin against MG S6 in artificial medium and chicken serum were determined. In vitro time-killing curves were established according to a series of multiples of the MIC value in an artificial medium, and ex vivo time-killing curves were established in serum samples obtained from infected chickens at different time points after oral administration with an initial titer of 1 × 10(6) color change units (CCU)/mL MG S6. The sigmoid Emax model was used to provide 24 h area under concentration-time curve/minimum inhibitory concentration ratios (AUC0-24h/MIC) for mycoplasmastasis, mycoplasmacidal activity and mycoplasmal elimination, respectively. The inoculum size and micro or macro methods exhibited little effect on MIC determination of MG, whereas matrix had a large effect. The rapid killing activity observed in in vitro time-killing curves seems to indicate that valnemulin was mycoplasmacidal and concentration dependent against MG. The AUC0-24h/MIC ratio for mycoplasmacidal activity and mycoplasmal elimination was 1321 h and 1960 h, respectively. A dosage regimen of 12.4 mg/kg/day and 18.3 mg/kg/day valnemulin was calculated for mycoplasmacidal activity and mycoplasmal elimination against MG S6, respectively.
College of Veterinary Medicine, National Reference Laboratory of Veterinary Drug Residues (SCAU), South China Agricultural University, Guangzhou, 510642, China.
Xia
X
Xiao
College of Veterinary Medicine, National Reference Laboratory of Veterinary Drug Residues (SCAU), South China Agricultural University, Guangzhou, 510642, China.
Jian
J
Sun
College of Veterinary Medicine, National Reference Laboratory of Veterinary Drug Residues (SCAU), South China Agricultural University, Guangzhou, 510642, China.
Yi
Y
Chen
College of Veterinary Medicine, National Reference Laboratory of Veterinary Drug Residues (SCAU), South China Agricultural University, Guangzhou, 510642, China.
Mengting
M
Zou
College of Veterinary Medicine, National Reference Laboratory of Veterinary Drug Residues (SCAU), South China Agricultural University, Guangzhou, 510642, China.
Dong-Hao
DH
Zhao
College of Veterinary Medicine, National Reference Laboratory of Veterinary Drug Residues (SCAU), South China Agricultural University, Guangzhou, 510642, China. Electronic address: gale@scau.edu.cn.
Ya-Hong
YH
Liu
D000284:Administration, Oral; D000818:Animals; D000900:Anti-Bacterial Agents / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology; D019540:Area Under Curve; D002645:Chickens / Q000097:blood; D004224:Diterpenes / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology; D004926:Escherichia coli; D004927:Escherichia coli Infections / Q000150:complications / Q000382:microbiology / Q000662:veterinary*; D006207:Half-Life; D008826:Microbial Sensitivity Tests; D009175:Mycoplasma Infections / Q000150:complications / Q000382:microbiology / Q000662:veterinary*; D045686:Mycoplasma gallisepticum / Q000187:drug effects*; D011201:Poultry Diseases / Q000097:blood / Q000188:drug therapy / Q000382:microbiology*
D000900:Anti-Bacterial Agents; D004224:Diterpenes; C117845:valnemulin
Chicken; Mycoplasma gallisepticum (MG); PK/PD; Valnemulin