title: Dose Assessment of Cefquinome by Pharmacokinetic/Pharmacodynamic Modeling in Mouse Model ofStaphylococcus aureusMastitis.
abstract: This work aimed to characterize the mammary gland pharmacokinetics of cefquinome after an intramammary administration and integrate pharmacokinetic/pharmacodynamic model. The pharmacokinetic profiles of cefquinome in gland tissue were measured using high performance liquid chromatograph. Therapeutic regimens covered various dosages ranging from 25 to 800 μg/gland and multiple dosing intervals of 8, 12, and 24 h. Thein vivobacterial killing activity elevated when dosage increased or when dosing intervals were shortened. The best antibacterial effect was demonstrated by a mean 1.5 log10CFU/gland visible count reduction. On the other hand, the results showed that the percentage of time duration of drug concentration exceeding the MIC during a dose interval (%T > MIC) was generally 100% because of the influence of drug distribution caused by the blood-milk barrier. Therefore, pharmacokinetic/pharmacodynamic parameter of the ratio of area under the concentration-time curve over 24 h to the MIC (AUC0-24/MIC) was used to describe the efficacy of cefquinome instead of %T > MIC. When the magnitude of AUC0-24/MIC exceeding 16571.55 h⋅mL/g, considerable activity of about 1.5 log10CFU/g gland bacterial count reduction was observedin vivo. Based on the Monte Carlo simulation, the clinical recommended regimen of three infusions of 75 mg per quarter every 12 h can achieve a 76.67% cure rate in clinical treatment of bovine mastitis caused byStaphylococcus aureusinfection.
authors: National Risk Assessment Laboratory for Antimicrobial Resistance of Animal Original Bacteria, South China Agricultural UniversityGuangzhou, China; Guangdong Provincial Key Laboratory of Veterinary Pharmaceutics, Development and Safety Evaluation, South China Agricultural UniversityGuangzhou, China.
authors: Yang
authors: Y
authors: Yu
authors: National Risk Assessment Laboratory for Antimicrobial Resistance of Animal Original Bacteria, South China Agricultural UniversityGuangzhou, China; Guangdong Provincial Key Laboratory of Veterinary Pharmaceutics, Development and Safety Evaluation, South China Agricultural UniversityGuangzhou, China.
authors: Yu-Feng
authors: YF
authors: Zhou
authors: National Risk Assessment Laboratory for Antimicrobial Resistance of Animal Original Bacteria, South China Agricultural UniversityGuangzhou, China; Guangdong Provincial Key Laboratory of Veterinary Pharmaceutics, Development and Safety Evaluation, South China Agricultural UniversityGuangzhou, China.
authors: Xiao
authors: X
authors: Li
authors: National Risk Assessment Laboratory for Antimicrobial Resistance of Animal Original Bacteria, South China Agricultural UniversityGuangzhou, China; Guangdong Provincial Key Laboratory of Veterinary Pharmaceutics, Development and Safety Evaluation, South China Agricultural UniversityGuangzhou, China.
authors: Mei-Ren
authors: MR
authors: Chen
authors: Defense Threat Reduction Agency, Fort Belvoir VA, USA.
authors: Gui-Lin
authors: GL
authors: Qiao
authors: National Risk Assessment Laboratory for Antimicrobial Resistance of Animal Original Bacteria, South China Agricultural UniversityGuangzhou, China; Guangdong Provincial Key Laboratory of Veterinary Pharmaceutics, Development and Safety Evaluation, South China Agricultural UniversityGuangzhou, China.
authors: Jian
authors: J
authors: Sun
authors: National Risk Assessment Laboratory for Antimicrobial Resistance of Animal Original Bacteria, South China Agricultural UniversityGuangzhou, China; Guangdong Provincial Key Laboratory of Veterinary Pharmaceutics, Development and Safety Evaluation, South China Agricultural UniversityGuangzhou, China.
authors: Xiao-Ping
authors: XP
authors: Liao
authors: National Risk Assessment Laboratory for Antimicrobial Resistance of Animal Original Bacteria, South China Agricultural UniversityGuangzhou, China; Guangdong Provincial Key Laboratory of Veterinary Pharmaceutics, Development and Safety Evaluation, South China Agricultural UniversityGuangzhou, China; College of Veterinary Medicine, National Reference Laboratory of Veterinary Drug Residues, South China Agricultural UniversityGuangzhou, China.
authors: Ya-Hong
authors: YH
authors: Liu
keywords: Monte Carlo simulation; PK/PD; cefquinome; dose assessment; mastitis