盐酸多西环素对鸡白痢和禽霍乱的疗效试验

以诺氟沙星为对照药物,研究了盐酸多西环素治疗鸡白痢病和禽霍乱的效果.结果盐酸多西环素对鸡白痢的治疗效果显著好于诺氟沙星,治愈率、死亡率差异显著（P＜0.05）;盐酸多西环素对禽霍乱的治疗效果好于诺氟沙星,治愈率差异不显著（P＞0.05）,而死亡率差异显著（P＜0.05）.     

Feline chlamydiosis

Chlamydiae are an important cause of acute and chronic conjunctivitis in cats. Until recently, only one organism was thought to infect cats, Chlamydophila felis (previously Chlamydia psittaci var. felis). Recently, other Chlamydia-like organisms belonging to the family Parachlamydiaceae, which comprises organisms that reside and proliferate within free-living amoeba, have been identified in cats with neutrophilic and eosinophilic conjunctivitis. The relative importance of these organisms and their amoebic hosts requires investigation. There is also weak evidence that chlamydiae may also be capable of causing reproductive tract disease and lameness in cats. Diagnosis of chlamydial conjunctivitis requires use of specialized culture techniques or the polymerase chain reaction. The antibiotic of choice to treat these infections is doxycycline; azithromycin is less effective. All cats in the household should be treated simultaneously. The zoonotic potential of these organisms appears low, but some precaution is warranted when handling affected cats.     

Orally administered doxycycline accumulates in synovial fluid compared to plasma

Reasons for performing study: Tetracycline compounds have been used to slow the progression of osteoarthritis (OA) and rheumatoid arthritis but the concentration of doxycycline attained in synovial fluid following oral, low‐dose administration has yet to be determined. Objective: To determine the concentration of doxycycline in synovial fluid following oral, low‐dose administration. Methods: Six mature horses received doxycycline (5 mg/kg bwt q. 12 h for 5 doses). Venous blood and synovial fluid samples were collected at t = 0, 0.25, 0.5, 1, 12, 24, 48 and 72 h. Doxycycline concentrations were measured using reverse phase high pressure liquid chromatography with ultraviolet detection. Results: Doxycycline concentrations at all time points after t = 0 were above the lower limit of quantification for the assay. Plasma concentrations of doxycycline were above 0.21 µg/ml at t = 0.5 h. The mean ± s.d. peak concentration (C_max) of doxycycline in plasma was 0.37 ± 0.22 µg/ml and time to peak concentration was 0.54 ± 0.19 h. Synovial fluid concentrations of doxycycline were above 0.12 µg/ml 1 h after drug administration. The mean C_max of doxycycline in the synovial fluid was 0.27 ± 0.10 µg/ml. The penetration factor of doxycycline from plasma into synovial fluid, as determined by a ratio of the area‐under‐the‐curve for synovial fluid:plasma during the sampling period, was 4.6. Potential relevance: Orally administered doxycycline distributes easily into synovial fluid with a penetration factor of 4.6. Terminal half‐life of the drug in synovial fluid was longer than in the plasma, indicating possible accumulation in this compartment. Further in vivo studies are warranted to define a medication protocol prior to routine clinical use of doxycycline for the treatment of OA.     

一种温敏型凝胶子宫灌注液的制备及药物浓度的监测

目的 研制一种多西环素温敏型原位凝胶子宫灌注液,并对其进行质量评价及子宫内药物浓度的监测。方法 以泊洛沙姆407(P407)和泊洛沙姆188(P188)为主要温敏材料,采用“冷法”工艺制备原位凝胶。采用单因素分析和正交试验对处方进行筛选与优化,通过无膜溶出模型考察制剂体外溶蚀和释药情况,并在高温、高湿、强光等条件下对研制的温敏凝胶稳定性进行考察。选用5头二元杂交母猪对制剂进行子宫内药物浓度的监测。结果 最终优化处方为50 g制剂含多西环素1 g、P407 10 g、P188 2.5 g、氯化镁2.3 g和亚硫酸氢钠0.1 g,用乙醇胺调pH至4.0±0.2,余量为超纯水。制剂体外溶蚀及释药时间长达48 h,累积溶蚀率和释药率均达100%。制剂稳定性符合兽用化学药物稳定性研究技术指导原则的要求,在第2次给药96 h后母猪子宫内药物浓度仍能保持在68.54 μg/mL。结论 多西环素温敏型原位凝胶子宫灌注液制备方法简单,性质稳定,猪子宫灌注给药后局部药物浓度长时间维持在较高水平,具有缓释效果,有望为临床治疗母猪子宫内膜炎开创新途径。     

一种检验长效多西环素注射剂安全性的方法

介绍了用肌肉(血管)刺激性试验来测定长效多西环素注射剂安全性的方法,应用该方法的试验结果表明,20%浓度的长效多西环素注射剂的局部试验对动物肌肉血管的刺激性较弱,符合安全性试验标准。     

饲料中3种四环素类药物的高效毛细管电泳检测方法

作者建立了鸡饲料中四环素、土霉素和多西环素的高效毛细管电泳检测方法。3种药物在40 mmol/L磷酸氢二钠—20 mmol/L柠檬酸(pH 2.6)的电泳缓冲液、30 kV的分离电压、长度64.5 cm、内径75 μm的毛细管内得到完全分离。在1～80 mg/kg范围内3种药物线性良好,R2>0.994;配合饲料和预混料中3种药物的定量限分别为2和4 mg/kg;添加回收试验回收率>80%,方法的日内变异系数和日间变异系数均<10%。     

盐酸多西环素临床治疗异育银鲫嗜水气单胞菌感染的给药方案的制定

通过高效液相色谱法(HPLC法)测定盐酸多西环素在异育银鲫(Carassius auratus gibelio)血清中不同时间点的血药浓度,并结合药物的体外药效学参数,确定该药的临床给药方案。结果显示,盐酸多西环素对嗜水气单胞菌(Aeromonas hydrophila,AH10)的最小抑菌浓度(MIC)为0.4μg/m L,最小杀菌浓度(MBC)为3.2μg/m L,防耐药突变浓度(MPC)为4.8μg/m L,耐药选择窗(MSW)为0.4~4.8μg/m L。盐酸多西环素的抗菌后效应(PAE)约为2 h;在异育银鲫中能够达到良好的抑菌杀菌效果的盐酸多西环素口灌剂量是20 mg/kg,休药期至少为25 d;能够控制耐药菌株产生的盐酸多西环素口灌剂量是80 mg/kg,休药期至少为60 d。     

基于偏最小二乘回归同时测定阿莫西林和多四环素含量

阿莫西林和多四环素在紫外光谱区间吸收峰附近有多重共线现象,紫外分光光度法难以准确测出2种物质各自含量.本文通过L16(45)正交实验设计,采集200~250 nm波长混合样品吸收光谱,数据经标准化处理,建立偏最小二乘回归预报数学模型.结果显示,该法计算阿莫西林和多四环素的预测相对误差(RPE)分别为3.13%和6.42%,平均加标回收率分别为100.34%和100.71%.该法简便快捷,准确可靠,样品无需预先分离.     

盐酸多西环素微囊制备及其在家兔体内的药动学研究

以可生物降解材料壳聚糖为囊材,采用乳化交联法制备盐酸多西环素壳聚糖微囊,考查其形态学特征、载药量、及体外释药情况等;将12只小鼠随机分为2组,每组6只,分别按药物剂量20 mg·kg-1灌胃,采用HPLC法,以C18为固定相,流动相为乙腈∶甲醇∶0.01 mol· L-1草酸溶液(2∶1∶7),在346 nm处对不同时间点的血药浓度进行检测,研究其在家兔体内药动学特征.结果成功制得外观较均一、光滑,平均粒径约10 μm,药物含量为20.60％,平均包封率为85.54％且具有明显缓释作用的盐酸多西环素微囊;家兔口服给药盐酸多西环素原药和微囊后主要药动学参数Cmax分别为(1.74士0.00)和(1.10士0.00)mg·L-1,Tmax分别为3和12 h,AUC(0-t)分别为(11.71±0.17)和(32.51士0.20) mg· L-1 ·h,T1/2.分别为(1.16士0.53)和(7.51士2.87)h,T1/2β分别为(2.19士0.38)和(9.00±1.60)h,相对生物利用度为289.4％,药时数据符合一级吸收二室模型.说明微囊化后的盐酸多西环素吸收、分布缓慢,生物利用度有了很大提高.