头孢喹肟是动物专用的第四代头孢菌素类药物，对大肠杆菌和金黄色葡萄球菌均有较好的作用效果。本研究旨在建立头孢喹肟对大肠杆菌和金黄色葡萄球菌的野生型折点（wild-type cut-off, CO_WT）和药动/药效学折点（pharmacokinetic/pharmacodynamic, CO_PD），以期为临床细菌耐药性监测提供数据指导。采用微量肉汤稀释法测定2014至2018年期间广东省分离的210株猪源大肠杆菌和160株猪源金黄色葡萄球菌对头孢喹肟的最低抑菌浓度（minimum inhibitory concentration, MIC），结果表明头孢喹肟对大肠杆菌的MIC₅₀（能抑制50%细菌生长的最低药物浓度和MIC₉₀（能抑制90%细菌生长的最低药物浓度）分别是0.06 μg mL^-1和0.25 μg mL^-1；对金黄色葡萄球菌的MIC₅₀和MIC₉₀分别是0.5 μg mL^-1 和1 μg mL^-1。统计学分析方法和ECOFFinder程序计算结果表明头孢喹肟对大肠杆菌和金黄色葡萄球菌的野生型折点分别为0.125 μg mL^-1和2 μg mL^-1。大肠杆菌和金黄色葡萄球菌对头孢喹肟的耐药率分别为11.9％和6.25％。基于5000次循环的蒙特卡洛计算结果显示在临床推荐给药剂量下（2 mg kg^-1,每天给药2次，连续给药3天），头孢喹肟对大肠杆菌和金黄色葡萄球菌的药动/药效学折点值均为0.25 µg mL^-1，表明在当前推荐剂量下可对MIC ≤ 0.25 μg mL^-1的大肠杆菌和金黄色葡萄球菌实现90％以上的有效治疗。当前的给药方案对金黄色葡萄球菌引起的感染不能取得理想的治疗效果，将头孢喹肟给药剂量调整为4.5 mg kg^-1时，能对MIC₉₀ = 1 μg mL^-1的金黄色葡萄球菌引起的感染实现90%以上的有效治疗。本研究对于临床上头孢喹肟对猪源大肠杆菌和金黄色葡萄球菌的耐药性监测和用药指导有重要意义。

The purpose of the study was to investigate the pharmacokinetics of cefquinome in plasma and milk samples of lactating Chinese Holstein following a single intramammary administration into one quarter at the dose of 75 mg. Residue depletion of cefquinome in milk administrated at one quarter following three consecutive infusions at the same dose were also carried out. Cefquinome concentrations in plasma and milk were determined by high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method. A non-compartmental analysis was used to obtain the pharmacokinetic parameters of cefquinome. Following the single treatment, cefquinome wasn’t detected in any of the plasma samples. The concentration of cefquinome in milk reached peaked values (Cmax) of (599.00±322.00) μg mL-1 at 2 h after administration (Tmax), elimination half-life (t1/2λz) was (4.63±0.26) h, area under the concentration-time curve (AUC0-∞) was (4 890.19±1 906.98) μg mL-1 h, and mean residence time (MRT) was (6.03±2.27) h. In residue depletion study, cefquinome concentrations in 5 out of 6 milk samples at 72 h were lower than the maximum residue limit fixed by the European regulatory agency (20 μg kg-1 for cefquinome) and cefquinome still could be detected in milk of treated quarters at 120 h post-treatment. The maximum concentration (Cmax) of cefquinome in milk from treated quarters was (486.50±262.92) μg mL-1 and arrived at 6 h after administration (Tmax), elimination half-life (t1/2λz) was (6.30±0.76) h, area under the concentration-time curve (AUC0-∞) was (44747.79±11434.43) μg mL-1 h, and mean residence time (MRT) was (10.09±1.40) h. This study showed that cefquinome has the feature of poor penetration into blood and was eliminated quickly from milk in lactating cows after intramammary administration.

The pharmacokinetics of quinocetone and its major metabolites in healthy swine was investigated in this paper.Quinocetone was administered to 8 healthy cross-bread swine intravenously and orally at a dosage of 4 and 40 mg kg-1body weight respectively in a randomized crossover design test with two-week washout period. A sensitive highperformanceliquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method was developed for thedetermination of quinocetone and its metabolite 1-desoxyquinocetone in plasma. Plasma concentration versus timeprofiles of quinocetone and its metabolite 1-desoxyquinocetone were analyzed by non-compartmental analysis usingWinnonlin 5.2 software. Mean maximum concentrations (Cmax) for quinocetone was found to be (0.56±0.13) μg mL-1 at 2.92 h,after oral administration of quinocetone. Mean maximum concentrations (Cmax) for 1-desoxyquinocetone after intravenousor oral administration of quinocetone were (0.0095±0.0012) μg mL-1 at 0.083 h and (0.0067±0.0053) μg mL-1 at 3.08 h. Theapparent elimination half-lives (T1/2) for quinocetone and its metabolite 1-desoxyquinocetone were (2.24±0.24) and(5.23±0.56) h after intravenous administration of quinocetone and (2.91±0.29) and (11.85±2.89) h after oral administrationof quinocetone, respectively. Mean areas under the plasma concentration-time curve (AUC0- ) for quinocetone and 1-desoxyquinocetone were (2.02±0.15) and (0.2±0.002) μg h mL-1 respectively after intravenous administration of quinocetone,and (3.5±0.79) and (0.053±0.03) μg h mL-1 after oral administration of quinocetone, respectively. Quinocetone was rapidlyabsorbed and metabolized in swine after oral and intravenous administration. The plasma concentration-time curve(AUC0- ) of 1-desoxyquinocetone were much smaller than those of quinocetone, while the elimination half-lives (T1/2) weremuch longer than those of quinocetone after intravenously (i.v.) or oral administration.

The present study was carried out to investigate the pharmacokinetics of mequindox (MEQ), a new synthetic quinoxaline 1,4-dioxide derivative and its two main metabolites M1 [2-isoethanol mequinoox], M2 [2-isoethanol 1-desoxymequindox] in healthy swine. MEQ (10 mg kg-1 body weight) was administered to nine healthy cross-bread swine via oral, intramuscular, and intravenous routes in a randomized 3×3 crossover design with a 1-wk washout period. A sensitive high-performance liquid chromatography (HPLC) method was used for the determination of plasma concentrations of MEQ and its metabolites M1 and M2. Plasma concentration versus time profiles of MEQ and its metabolites, M1 and M2, were analyzed by noncompartmental analysis using WinNonlin 5.2 software. The mean maximum concentrations (Cmax) of M1 and M2 after intravenous administration of MEQ were (5.27±1.59) μg mL-1 at 1.78 h and (1.01±0.29) μg mL-1 at 0.92 h, respectively. The mean maximum concentrations (Cmax) of MEQ, M1, and M2 were found to be (6.96±3.23), (6.61±1.56), and (0.78 ±0.25) μg mL-1, respectively at 0.15, 1.61, and 1.30 h after intramuscular administration of MEQ, respectively and (0.75±0.45), (6.90±1.52), and (0.62±0.21) μg mL-1, respectively at 0.40, 1.57, and 2.00 h, respectively after oral administration of MEQ. The apparent elimination half-lives (t1/2) of MEQ, M1, and M2 were (0.84±0.35), (7.57±3.93), and (9.56±6.00) h, respectively after intravenous administration of MEQ; (0.50±0.25), (6.30±3.00), and (5.94±2.54) h, respectively after intramuscular administration of MEQ; and (1.64±1.17), (5.59±1.93), and (16.25±10.27) h , respectively after oral administration of MEQ. The mean areas under the plasma concentration-time curve (AUC0- ) of MEQ, M1, and M2 were (4.88±1.54), (36.93±17.50), and (5.16±1.94) μg h mL-1, respectively after intravenous administration of MEQ; (4.18±0.76), (48.25±20.82), and (4.88±2.21) μg h mL-1 , respectively after intramuscular administration of MEQ; and (1.01±0.40), (48.83±20.71), and (5.54±2.23) μg h mL-1, respectively after oral administration of MEQ. MEQ was rapidly absorbed and metabolized in swine after oral, intramuscular, and intravenous administration. Further studies are required to investigate the double-peak phenomenon observed in the plasma concentration-time profile after oral administration and the pharmacokinetics of other metabolites of MEQ.