AUTHOR=Yu Yang , Zhou Yu-Feng , Li Xiao , Chen Mei-Ren , Qiao Gui-Lin , Sun Jian , Liao Xiao-Ping , Liu Ya-Hong 

TITLE=Dose Assessment of Cefquinome by Pharmacokinetic/Pharmacodynamic Modeling in Mouse Model of Staphylococcus aureus Mastitis

JOURNAL=Frontiers in Microbiology

VOLUME=7

YEAR=2016

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2016.01595

DOI=10.3389/fmicb.2016.01595

ISSN=1664-302X

ABSTRACT=<p>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. The <italic>in vivo</italic> bacterial killing activity elevated when dosage increased or when dosing intervals were shortened. The best antibacterial effect was demonstrated by a mean 1.5 log<sub>10</sub>CFU/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 &gt; 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 (AUC<sub>0-24</sub>/MIC) was used to describe the efficacy of cefquinome instead of %T &gt; MIC. When the magnitude of AUC<sub>0-24</sub>/MIC exceeding 16571.55 h⋅mL/g, considerable activity of about 1.5 log<sub>10</sub>CFU/g gland bacterial count reduction was observed <italic>in vivo</italic>. 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 by <italic>Staphylococcus aureus</italic> infection.</p>