不同给药方式下培氟沙星在鲤体内的药代动力学研究

在水温为18℃下,按10 mg/kg（体质量）对体质量为（200±30）g的福瑞鲤Cyprinus carpio单次肌肉注射和混饲口灌培氟沙星,于不同时间点采集鲤血浆、肌肉、肝胰脏、肾脏组织,经超高液相色谱法测定各组织中培氟沙星的浓度,并采用DAS 3.0药物代谢动力学软件的非房室模型统计矩方法分析药时数据。结果表明：混饲口灌给药和肌注给药后,培氟沙星的药时曲线下面积（ AUC）分别为88.35、139.9 mg·h/L,达峰浓度（ Cmax ）分别为2.092、3.687 mg/L,达峰时间（ Tmax ）分别为4.0、0.5 h,消除半衰期（ t1/2）分别为22.301、74.357 h,表观分布容积（ Vd ）分别为5.464、15.342 L/kg,总体清除率（ CL ）分别为0.170、0.143 L·kg/h。研究表明,肌肉注射给药较混饲口灌达峰时间短,达峰浓度高,半衰期长,生物利用度高。     

表面等离子共振生物传感器检测培氟沙星的方法研究

研究表面等离子共振生物传感器检测缓冲液中培氟沙星的方法,为样品的检测提供依据。采用抑制法,将培氟沙星与卵清蛋白的偶联物固定在芯片上,将抗体与不同浓度的培氟沙星混合后通入芯片表面,优化反应条件,构建标准曲线。结果显示,选择1∶1000稀释的抗体,流速7 μL/min,反应时间4 min,构建标准曲线,可以达到较低的检测限。利用SPR生物传感器建立快速检测缓冲液中培氟沙星的方法,检测限为0.8 ng/mL,检测时间为4 min,为样品检测奠定基础。     

甲磺酸培氟沙星对体外鸡毒支原体的抑菌试验和对鸡毒支原体病的治疗试验

利用甲磺酸培氟沙星水溶性粉剂对鸡毒支原体分别进行体内外的抑菌治疗试验。体外抑菌试验结果表明：该药物能有效地抑制试管中鸡毒支原体的生长繁殖。体内试验结果表明：当饮水中药物浓度达到１００ｍｇ／Ｌ时,能有效地防止由于鸡毒支原体引起的死亡;当饮水中药物浓度达到５０ｍｇ／Ｌ以上时,能明显地减轻以至部分消除鸡毒支原体强毒引起的气囊损伤;和感染不治疗对照组相比,该药物能提高鸡体增重;用甲磺酸培氟沙星治疗,能抑制感染鸡体内的鸡毒支原体,从而使部分鸡体内检测不到鸡毒支原体抗体。     

长效沙星注射液的化学稳定性试验

为了进一步为长效沙星(培氟沙星)注射液的临床应用提供依据,以二蒸水为溶剂,采用紫外-可见分光光度法,在190~400 nm波长范围内进行全波段扫描,以最大吸收波长确定为培氟沙星的测定波长,最后以光加速试验和经典恒温热加速试验考察了长效沙星注射液的稳定性。结果表明,培氟沙星的测定波长为274 nm,在2~10μg/mL质量浓度范围内,长效沙星溶液的吸光度与其质量浓度之间有良好的线性关系,平均回收率为100.43%。长效沙星注射液对热稳定,对光不稳定,在避光、室温(25℃)条件下的有效期暂定为2年。     

Pharmacokinetics of Pefloxacin in Goats after Intravenous or Oral Administration

The plasma concentrations and pharmacokinetics of the fluoroquinolone antimicrobial agent pefloxacin, following the administration of a single intravenous (10 mg/kg) or oral (20 mg/kg) dose, were investigated in healthy female goats. The antimicrobial activity in plasma was measured at predetermined times after drug administration by an agar well diffusion microbiological assay, using Escherichia coli (ATCC 25922) as the test organism. Concentrations of the drug 0.25 g/ml were maintained in plasma for up to 6 and 10 h after intravenous (IV) or oral administration of pefloxacin, respectively. The concentration–time data for pefloxacin in plasma after IV or oral administration conformed to two- and one-compartment open models, respectively. Plasma pefloxacin concentrations decreased rapidly during the initial phase after IV injection, with a distribution half-life (t _1/2 ) of 0.10±0.01 h. The terminal phase had a half-life (t _1/2 ) of 1.12±0.21 h. The volume of distribution at steady state (V _dss), mean residence time (MRT) and total systemic clearance (Cl_B) of pefloxacin were 1.08±0.09 L/kg, 1.39±0.23 h and 821±88 (ml/h)/kg, respectively. Following oral administration of pefloxacin, the maximum concentration in the plasma (C _max) was 2.22±0.48 g/ml and the interval from administration until maximum concentration (t _max) was 2.3±0.7 h. The absorption half-life (t _{1/2 ka}), mean absorption time (MAT) and elimination half-life of pefloxacin were 0.82±0.40, 4.2±1.0 and 2.91±0.50 h, respectively. The oral bioavailability of pefloxacin was 42%±5.8%. On the basis of the pharmacokinetic data, a dosage regimen of 20 mg/kg, IV at 8 h intervals or orally twice daily, is suggested for treating infections caused by drug-sensitive pathogens in goats.     

Disposition Kinetics and Urinary Excretion of Pefloxacin after Intravenous Injection in Crossbred Calves

The disposition kinetics and urinary excretion of pefloxacin after a single intravenous administration of 5 mg/kg were investigated in crossbred calves and an appropriate dosage regimen was calculated. At 1 min after injection, the concentration of pefloxacin in the plasma was 18.95±0.892 g/ml, which declined to 0.13±0.02 g/ml at 10 h. The pefloxacin was rapidly distributed from the blood to the tissue compartment as shown by the high values for the initial distribution coefficient, (12.1±1.21 h^–1) and the constant for the rate of transfer of drug from the central to the peripheral compartment, K ₁₂ (8.49±0.99 h^–1). The elimination half-life and volume of distribution were 2.21±0.111 h and 1.44±0.084 L/kg, respectively. The total body clearance (Cl_B) and the ratio of the drug present in the peripheral to that in the central compartment (P/C ratio) were 0.454±0.026 L/kg h) and 5.52±0.519, respectively. On the basis of the pharmacokinetic parameters obtained in the present study, an appropriate intravenous dosage regimen for pefloxacin in cattle for most of the bacteria sensitive to it would be 6.4 mg/kg repeated at 12 h intervals.     

Effect of trikatu pretreatment on the pharmacokinetics of pefloxacin administered orally in mountain Gaddi goats

The pharmacokinetics of orally administered pefloxacin were studied to evaluate the bio-enhancing effect of the herbal bio-enhancer, trikatu, in mountain Gaddi goats (n = 6). The findings of the study revealed a decreased plasma concentration (p > 0.05) of pefloxacin following trikatu administration during the absorption phase (10, 15, 20 min post pefloxacin administration). In contrast, the plasma concentrations of pefloxacin were significantly higher at 4, 6, 8 and 12 h (during the elimination phase) of the pefloxacin administration. The findings of the investigation revealed higher values for the area under the curve, the area under the first moment of the plasma drug concentration time curve, the mean residential time, the total duration of pharmacological action and bioavailability. Trikatu treatment, however, significantly reduced the elimination half life (t_1/2β) and zero time intercept of the elimination phase. The apparent volume of distribution based on the total area under the plasma drug concentration curve [(Vd_(area)] and the apparent volume of distribution based on the zero time plasma concentration intercept of the elimination phase [Vd_(B)] were significantly higher in trikatu treated animals indicating a better penetration of the drug. Based on the MIC of 0.8 µg/ml of pefloxacin, a priming dose of 6.0 mg/kg and a maintenance dose of 2.21 mg/kg is required to be administered at 8 h intervals. For practical purposes in goats this would mean a priming dose of 6 mg/kg and a maintenance dose of 2 mg/kg given by the oral route, to be repeated at 8 h intervals.     

Some Pharmacokinetic Parameters of Pefloxacin in Lactating Goats

The aim of this study was to elucidate some of the pharmacokinetic parameters of pefloxacin in lactating goats (n = 5) following intravenous (i.v.) or intramuscular (i.m.) injections of 10 mg/kg bw. Serially obtained serum, milk and urine samples were collected at precise time intervals, and the drug concentrations were assayed using a microbiological assay. A two-compartment open model best described the decrease of pefloxacin concentration in the serum after intravenous administration. The maximum serum concentration (C _p ⁰ ) was 8.4±0.48 g/ml; elimination half-life (t _1/2) was 1.6±0.3 h; total body clearance (Cl_tot) was 3.6±0.3 L/kg/h; steady-state volume of distribution (V _dss) was 5.14±0.21 L/kg; and the area under the curve (AUC) was 2.78±0.22 g.ml/h. Pefloxacin was absorbed rapidly after i.m. injection with an absorption half-life (t _1/2ab) of 0.32±0.02 h. The peak serum concentration (C _max) of 0.86±0.08 g/ml was attained at 0.75 h (T _max). The absolute bioavailability after i.m. administration was 70.63±1.13% and the serum protein-bound fraction ranged from 7.2% to 14.3%, with an average value of 9.8±1.6%. Penetration of pefloxacin from the blood into the milk was rapid and extensive, and the pefloxacin concentration in milk exceeded that in serum from 1 h after administration. The drug was detected in milk and urine for 10 and 72 h, respectively; no samples were taken after 72 h.     

HPLC-PDA法测定氟苯尼考注射液、柴胡注射液中非法添加培氟沙星、洛美沙星

建立了氟苯尼考注射液、柴胡注射液中非法添加培氟沙星、洛美沙星的HPLC-PDA检查方法。采用十八烷基硅烷键合硅胶为填充剂;以磷酸溶液-乙腈-甲醇(85.5∶7.0∶7.5)为流动相;二极管阵列检测器,提取波长为277 nm。通过液相色谱保留时间、峰纯度检查和光谱相似度检查对非法添加物进行确证。结果表明,该色谱条件下培氟沙星、洛美沙星与其他物质分离良好。培氟沙星在氟苯尼考注射液、柴胡注射液中的平均回收率分别为101.4%(RSD=0.2%)、100.0%(RSD=0.4%),洛美沙星在氟苯尼考注射液、柴胡注射液中的平均回收率分别为101.2%(RSD=0.1%)、99.8%(RSD=0.5%)。本方法简便、准确、可靠,可用于检查氟苯尼考注射液、柴胡注射液中非法添加的培氟沙星、洛美沙星。