单诺沙星（Danofloxacin）在雏鸡体的组织动力学及残留

以高效液相色谱法为定量手段 ,研究了单诺沙星 (danofloxacin)在雏鸡体内的组织动力学特征 ,并采用回归分析法研究了血药浓度与组织药物浓度间的相关性。6 0只雏鸡口服单诺沙星 (5 m g/ kg)后 ,血浆的药时数据符合一级吸收二室模型。肝脏、肾脏、心脏、肺脏的药时数据符合一级吸收三项指数方程 ;心脏的药时数据符合一级吸收二项指数方程。血浆、肝脏、肾脏、心脏、肺脏及肌肉的主要动力学参数是 :t1 /2 ka分别为 0 .2 42 8、0 .35 2 4、0 .35 41、0 .2 6 43、0 .3377、0 .2 5 36 h、t1 /2α分别为 0 .8917、1.12 12、0 .7189、1.6 142、0 .44 37h(缺肌肉的 t1 /2α) ,t1 /2β分别为 8.7936、3.6 0 2 5、4.45 70、10 .2 940、4.32 83、5 .95 78h,Tp分别为 0 .9377、1.0 6 6 5、0 .936 2、0 .9993、0 .996 2、1.4381h,Cmax分别为0 .5 487、 2 .8419、 2 .42 95、 0 .2 6 6 8、 1.70 42、 0 .2 72 6 m g/ L ,AUC分别为 3.0 5 2 3、 13.5 86 0、 10 .4180、 2 .15 2 1、9.6 888、2 .715 7mg/ (L· h) ,Tcp分别为 12 .6 130、18.0 730、18.8790、8.0 5 5 7、19.6 930、13.86 0 0 h。研究结果表明 ,组织中的药物浓度以肝脏、肾脏最高 ,其次是肺脏 ,均显著高于血浆中的药物浓度 ,心脏、肌肉中的浓度最低 ,血浆     

达氟沙星对试验性感染仔猪副伤寒和霉形体肺炎的药效学研究

研究了国产新兽药达氟沙星对人工感染仔猪伤寒和霉形体肺炎的疗效。每个疗效试验用仔猪105只，随机分为达氟沙星3个不同剂量组，恩诺沙星对照组，强力霉素对照组，阳性对照组和阴性对照组，每组动物15只。当感染猪出现典型症状时，达氟沙星3个剂量组分别按每千克体重2．5ml,1.25mg,0.625mg，0.625mg及恩诺沙星组按2．5mg肌肉注射，每日2次，强力霉素按每千克体重3mg肌肉注射，每日2次。结果表明：达氟沙星3个不同剂量组、恩诺沙星组、强力霉素组连续用药4d，对仔猪副伤寒的治愈率分别是100％、80％、33．3％、80％、53．3％、而感染（阳性）对照组的死亡率为66．7％；达氟沙星3个不同剂量组、恩诺沙星组、强力霉素组连续用药5d,对霉形体肺炎的治愈率分别是100％、80％、93．3％，肺部病变率分别是20％、40％、60％、20％、60％，而感染（阳性）对照组的死亡率为40％，肺部病变率为1005。     

单诺沙星对昆明种小白鼠的亚急性毒性研究

以昆明种小白鼠为实验研究，进行了单诺沙星的亚急性毒性研究。小白鼠分为4组，1－3组为试验组，分别以20，50，100mg/kg体重单诺沙星溶于饮水中连续给药一个月，第4组为对照组。实验期间定期称量小白鼠在给药期内的体重和采食量，计算食饵效率，并在给药半个月和一个月时分两次检查各组小白鼠的器官系数与器官含水量、血常规、肝肾功能指标GPT、GOT、AKP、Cr、BUN以及心、肝、脾、肺、肾、脑的病理组织学变化。实验结果表明：高剂量组小白鼠表现的毒性反应较轻，且这种毒性反应没有随时间的延长而加剧。中、低剂量组小白鼠没有出现明显的毒性反应。表明单诺沙星的毒性较低。     

猪肉组织中氟喹诺酮类药物残留检测

随机选取本实验室内的8名化验员,分别测定猪肉组织中氟喹诺酮类药物残留量,通过对结果数据的分析,得出本实验室测定结果的准确程度。通过磷酸盐缓冲溶液提取猪肉组织中的氟喹诺酮类药物残留,经C18柱净化后,用高效液相色谱法测定含量。环丙沙星、达氟沙星、恩诺沙星和沙拉沙星的平均回收率（%）分别为：95.6、86.9、89.3和95.6,批内变异系数均≤14%,批间变异系数均≤6%。结果数据满足标准要求,证明本实验室能准确开展此项检测活动。     

Some Pharmacokinetic Data for Danofloxacin in Healthy Goats

The pharmacokinetics of danofloxacin was determined in five clinically normal adult female goats after intravenous (IV) or intramuscular (IM) doses of 1.25 mg/kg body weight. Blood and urine samples were collected from each animal at precise time intervals. Serum and urine concentrations were determined using microbiological assay methods and the data were subjected to kinetic analysis. After intravenous injection, the serum concentration–time curves of danofloxacin were characteristic of a two-compartment open model. The drug was rapidly distributed and eliminated with half-lives of 17.71±1.38 min and 81.18±3.70 min, respectively. The drug persisted in the central, highly perfused organs with a K ₁₂/K ₂₁ ratio of 0.67±0.25. The mean volume of distribution at a steady state (V _dss) was 1.42±0.15 L/kg. After intramuscular administration, the serum concentration peaked after 0.58±0.04 h at approximately 0.33±0.01 g/ml. While danofloxacin could be detected in serum for 4 and 6 h, it was recovered in urine for up to 24 and 72 h after IV and IM administration, respectively. The systemic bioavailability after IM injection was 65.70%±10.28% and the serum protein-bound fraction was 13.55±1.78%.     

紫外分光光度法测定复方甲磺酸培氟沙星注射液含量

建立了复方甲磺酸培氟沙星注射液中甲磺酸培氟沙星与安乃近的含量测定方法.用紫外分光光度法中倍率减差法消除安乃近干扰,测定甲磺酸培氟沙星含量,检测波长为287、299 nm,溶剂为0.1 mol/L盐酸溶液;用紫外分光光度法中等波长消去法消除甲磺酸培氟沙星干扰,测定安乃近含量,检测波长为261、291 nm,溶剂仍为0.1 mol/L盐酸溶液;整个过程采用棕色容量瓶避光操作.测定甲磺酸培氟沙星含量的回归方程为:ΔA1＝0.089 936 C1,r1＝0.999 6,平均回收率99.66%,RSD=0.61%;测定安用近含量的回归方程为:ΔA2＝0.024 888 C2,r2＝0.999 6,平均回收率99.81%,RSD=0.41%.本方法简单、快速、易于操作.     

鲫血浆中甲磺酸达氟沙星的RP-HPLC法测定

建立了测定鲫血浆中甲磺酸达氟沙星浓度的反相高效液相色谱法(RP-HPLC).采用ZORBAX SB-C18色谱柱和SB-C18的保护柱;流动相:乙腈与磷酸盐缓冲液(含10 mmol.L-1磷酸二氢钠和15 mmol.L-1四丁基溴化铵,磷酸调节pH4.0)的体积比为8∶92;流速:1.0 mL.min-1;进样量:10μL;柱温:30℃;检测波长282 nm.内标物为盐酸氧氟沙星.本研究建立的甲磺酸达氟沙星标准曲线在0.05~5.00 mg.L-1范围内呈良好的线性关系(R=0.999 9),最低检测限为0.01 mg.L-1,提取回收率均大于80%,日内及日间相对标准偏差小于11%.     

三种兽用氟喹诺酮类药物对人工诱发鸡霍乱的疗效比较

采用试管肉汤两部类法,测得恩诺沙星、单诺沙星脑二氟沙星对鸡多杀性巴氏杆菌的最小抑菌质量浓度分别是０．０５、０．２及０．４ｍｇ／Ｌ,按５ｍｇ／ｋｇ的剂量,分别给人工诱发霍乱病鸡内服恩诺沙星、单诺沙星脏一氟沙星,每１２ｈ给药１次,连续３ｄ,这些药物对鸡霍乱的治愈率分别为９６．７％、８３．３％及８３．３％。而感染对照鸡的死亡率为１００％。     

Effect of phentolamine mesylate on regression of lidocaine–epinephrine epidural anaesthesia in sheep

ObjectiveTo determine the impact of epidural phentolamine on the duration of anaesthesia following epidural injection of lidocaine–epinephrine.Study designBlinded randomized experimental study.AnimalsA group of 12 adult ewes weighing 25.7 ± 2.3 kg and aged 8–9 months.MethodsAll sheep were administered epidural lidocaine (approximately 4 mg kg^–1) and epinephrine (5 μg mL^–1). Of these, six sheep were randomized into three epidural treatments, separated by 1 week, administered 30 minutes after lidocaine–epinephrine: SAL: normal saline, PHE1: phentolamine (1 mg) and PHE2: phentolamine (2 mg). The other six sheep were administered only epidural lidocaine–epinephrine: treatment LIDEP. Each injection was corrected to 5 mL using 0.9% saline. Noxious stimuli were pinpricks with a hypodermic needle and skin pinch with haemostatic forceps to determine the onset and duration of sensory and motor block. Heart rate, noninvasive mean arterial pressure (MAP), respiratory rate and rectal temperature were recorded.ResultsThe onset times were not different among treatments. Duration of sensory block was significantly shorter in SAL (57.5 ± 6.2 minutes), PHE1 (60.7 ± 9.0 minutes) and PHE2 (62.0 ± 6.7 minutes) than in LIDEP (81.7 ± 13.4 minutes) (p < 0.05). Duration of motor blockade was significantly shorter in PHE1 (59.4 ± 5.4 minutes) and PHE2 (54.3 ± 4.0 minutes) than in SAL (84.8 ± 7.0 minutes) and LIDEP (91.5 ± 18.2 minutes) (p < 0.01). MAP in PHE2 was decreased at 10 minutes after administration of phentolamine (p < 0.05).Conclusion and clinical relevanceEpidural administration of 5 mL normal saline after epidural injection of lidocaine–epinephrine reduced the duration of sensory but not motor block in sheep. Epidural administration of phentolamine diluted to the final volume of 5 mL diminished both the duration of sensory and motor block in sheep administered epidural lidocaine–epinephrine.     

Toxic effects of methylmercury,arsanilic acid and danofloxacin on the differentiation of mouse embryonic stem cells into neural cells

This study was performed to assess the neurotoxic effects of methylmercury, arsanilic acid and danofloxacin by quantification of neural-specific proteins in vitro. Quantitation of the protein markers during 14 days of differentiation indicated that the mouse ESCs were completely differentiated into neural cells by Day 8. The cells were treated with non-cytotoxic concentrations of three chemicals during differentiation. Low levels of exposure to methylmercury decreased the expression of GABA_A-R and Nestin during the differentiating stage, and Nestin during the differentiated stage. In contrast, GFAP, Tuj1, and MAP2 expression was affected only by relatively high doses during both stages. Arsanilic acid affected the levels of GABA_A-R and GFAP during the differentiated stage while the changes of Nestin and Tuj1 were greater during the differentiating stage. For the neural markers (except Nestin) expressed during both stages, danofloxacin affected protein levels at lower concentrations in the differentiated stage than the differentiating stage. Acetylcholinesterase activity was inhibited by relatively low concentrations of methylmercury and arsanilic acid during the differentiating stage while this activity was inhibited only by more than 40 µM of danofloxacin in the differentiated stage. Our results provide useful information about the different toxicities of chemicals and the impact on neural development.