盐酸头孢他美酯中有关物质测定研究

用高效液相色谱法测定盐酸头孢他美酯中的有关物质。对方法专属性、杂质峰归属、线性关系、灵敏度、重复性进行了系统的研究。本法对杂质能有效分离,线性关系ｒ＝０．９９９９,最低检测浓度为０．１ｕｇ／ｍｌ,重复性ＲＳＤ０．８３％。     

头孢妥仑匹酯在大鼠小肠中吸收代谢机制的初步研究

目的:探讨头孢妥仑匹酯(cefditoren pivoxil)在大鼠在体和离体小肠中代谢的吸收机制.方法:取Wistar大鼠随机分组,进行头孢妥仑匹酯在体肠袢吸收及应用酯酶抑制剂奥利司他(orlistat)后离体肠管温孵实验,采用HPLC梯度洗脱方法测定各肠溶液样品中头孢妥仑匹酯及头孢妥仑峰面积,验证头孢妥仑匹酯的吸收代谢机制.结果:头孢妥仑匹酯于大鼠在体及离体对照组肠溶液中0 min已有部分转化为头孢妥仑,于大鼠离体肠溶液中给酯酶抑制剂奥利司他后则于1 min后发生转化.结论:头孢妥仑匹酯于小肠吸收时,被小肠酯酶迅速水解成头孢妥仑,该作用可被酯酶抑制剂奥利司他所抑制.     

头孢特仑酯药物动力学及生物利用度研究

目的建立了人血浆中头孢特仑的HPLC方法,测定其片剂、干混悬剂的药物动力学参数及相对生物利用度。方法血样用甲醇沉淀、高速离心后进入液相分析,色谱柱:Agilent Zorbax C18(3.0 mm×150 mm,5μm),流动相为甲醇-水-HAC-TEA=35∶65∶0.6∶0.3,检测波长为262 nm。结果在0.047 5~4.75μg.mL-1峰面积值与浓度线性关系良好(r=0.999 9),定量下限为0.047 5μg.mL-1。绝对回收率为76.8%~83.3%。18名健康受试者随机交叉口服头孢特仑酯片剂、干混悬剂和进口头孢特仑酯片后,F0-τ分别为102.6%±13.4%和103.0%±8.8%。结论3种制剂生物等效。     

国产头孢他美酯治疗急性细菌感染临床研究

目的:通过随机对照和开放试验的方法评价国产头孢他美酯的临床疗效和安全性。方法:随机对照选用进口头孢他美酯作为对照组,每组各20例,开放组10例,均按500mg Bid给药,疗程7～14天。结果:国产头孢他美酯的临床治愈率75％(15/20),有效率90％(18/20),细菌清除率100％(18/18)。对照组分别为85％(17/20),90％(18/20),100％(16/16)。试验组 开放组分别为76.7％(23/30)、90％(27/30)、100％(26/26)。国产头孢他美酯和进口头孢他美酯不良反应发生率分别为3.33％和5％。以上结果经统计学处理差异无显著性(P>0.05)。结论:国产头孢他美酯是治疗呼吸道、泌尿道感染有效、安全的抗菌药物。     

Development of interpretive criteria for tebipenem disk diffusion susceptibility testing with <Emphasis Type="Italic">Staphylococcus</Emphasis> spp. and <Emphasis Type="Italic">Haemophilus influenzae</Emphasis>

Disk diffusion susceptibility interpretive criteria for tebipenem against Staphylococcus spp. and Haemophilus influenzae were developed using the Clinical and Laboratory Standards Institute (CLSI) guidelines. Tebipenem was tested by disk diffusion and broth microdilution methods against 119 clinical isolates of Staphylococcus spp. and 102 clinical isolates of H. influenzae. The zone diameters of 5-, 10-, and 30-μg disks were compared with broth microdilution minimum inhibitory concentration (MIC) results by scattergram and regression analysis. When the MIC breakpoint of 1 μg/ml was applied to the scattergrams, the 10-μg disk showed good correlation between the zone diameters and the MIC values. The corresponding disk diffusion zone diameter breakpoints with the 10-μg disk for Staphylococcus spp. were ≧22 mm (MIC ≦1 μg/ml) for susceptible, 20–21 mm (MIC = 2 μg/ml) for intermediate, and ≦19 mm (MIC ≧4 μg/ml) for resistant. We also proposed the breakpoint zone diameter of H. influenzae: ≧22 mm (MIC ≦1 μg/ml) for susceptible. These criteria demonstrated that the categorical agreements between disk diffusion and broth microdilution methods for Staphylococcus spp. and H. influenzae were 95.0% and 99.0%, respectively. The discrepancy rates of these criteria were acceptable to the CLSI guidelines.     

头孢他美酯干混悬剂致肝损伤一例

1例38岁女性患者因咳嗽、憋气、胸痛、发热给予安素美干混悬剂(头孢他美酯)0.36 g,2次/d,连续服用5 d后出现稀便及恶心症状。实验室检查结果为血WBC 9.52×109/L,E 0.30;生化检查:ALT 193 U/L、AST 83 U/L、ALP 117 U/L、GGT 57 U/L。结合其他检查,判断患者肺炎已基本痊愈;肝损伤可能由安素美干混悬剂引起,遂停用。同时,给予易善复0.456 g联合维生素C 0.2 g,3次/d,21 d后恢复正常。     

呼吸道苛养菌对头孢妥仑匹酯等10种抗菌药物的药敏监测

目的了解呼吸道感染苛养菌的分离及其对头孢妥仑匹酯等10种抗菌药物的药敏情况,为临床治疗提供参考。方法收集2005年、2007年、2008年及2010年1-6月从呼吸道细菌感染患者送检的痰标本中分离的苛养菌,采用美国临床实验室标准化研究所推荐的K B法检测头孢妥仑匹酯等10种抗菌药物对其的体外抗菌活性。结果438例患者共分离苛养菌462株,其产β 内酰胺酶率：流感嗜血杆菌23.62%（30/127）,副流感嗜血杆菌2.51%（5/199）,卡他莫拉菌41.58%（42/101）,未发现对青霉素中介或耐药的肺炎链球菌。流感嗜血杆菌、副流感嗜血杆菌、卡他莫拉菌及肺炎链球菌对头孢妥仑匹酯的敏感率分别为96.30%、94.36%、100.00%、100.00%;流感嗜血杆菌和副流感嗜血杆菌对头孢噻肟、头孢呋辛、头孢克罗、头孢唑林的敏感率为83.59%～93.33%,对阿莫西林/克拉维酸的敏感率分别为91.67%、88.21%;卡他莫拉菌、肺炎链球菌对阿莫西林/克拉维酸的敏感率为100.00%;对克拉霉素的敏感率,流感嗜血杆菌为87.96%,其他3种菌为34.29%～59.00%;4种苛养菌对四环素的敏感率较低,为22.86%～63.00%;流感嗜血杆菌、副流感嗜血杆菌、卡他莫拉菌对复方磺胺甲口恶唑的耐药率高,达54.63%～73.33%。结论头孢妥仑匹酯对呼吸道感染的苛养菌具有很强的抗菌活性;临床医生应根据药敏试验结果合理使用抗菌药物,以减少耐药菌的产生。     

HPLC法测定头孢特仑新戊酯片的含量

目的:建立头孢特仑新戊酯片含量测定的高效液相色谱方法.方法:采用岛津CLASS VP C18(250 mm×4.6 mm,5 μm)色谱柱;以乙腈:醋酸钠缓冲液(35∶65)为流动相;以对羟基苯甲酸甲酯为内标;检测波长 254 nm;调整流量使头孢特仑新戊酯峰的保留时间为 14 min.结果:头孢特仑新戊酯的线性范围为100～1000 μg·mL-1,r＝0.9999,平均回收率为99.63%,RSD为0.57%.结论:本法可用于头孢特仑新戊酯片的含量测定,操作简便,结果准确.     

泰比培南酯的合成工艺研究

目的 研究新型碳青霉烯类抗生素泰比培南酯的合成工艺。方法 以 (4R,5S,6S)-3-二苯基磷酰氧基-6-[(1R)-1-羟乙基]-4-甲基-7-氧代-1-氮杂双环[3.2.0]庚-2-烯-2-羧酸对硝基苄酯和3-巯基-1-(1,3-噻唑啉-2-基)氮杂环丁烷盐酸盐为起始原料,经过缩合、氢化、亲核取代3步反应,得到目标产物。结果与结论 目标化合物及中间体的结构经熔点、IR、MS、¹H-NMR和¹³C-NMR 谱确证。该合成工艺反应步骤少、操作简便、收率高、产品纯度高,有利于工业化生产。     

A Randomized, Double-blinded, Open Label Study of the Efficacy and Safety of Cefcapene Pivoxil and Amoxicillin·Clavulanate in Acute Presumed Bacterial Rhinosinusitis

Objectives

Currently established first line therapy of acute (presumed bacterial) rhinosinusitis (ARS) consists of 10 to 14 days of oral amoxicillin or cephalosporins. This study compared the clinical efficacy and tolerance of cefcapene pivoxil (CP) and amoxicillin-clavulanate (AMC) in patients with ARS.

Methods

A randomized, open labeled, double-blinded trial of ARS patients over 15 years of age was performed. Patients diagnosed with ARS received paranasal sinus X-rays and nasal endoscopies and 2 weeks of either CP (150 mg, 3 times/ day) or AMC (625 mg, amoxicillin 500 mg, 3 times/day). All patients revisited the clinic on days 7, 14, and 28 for evaluation of changes in symptoms, endoscopy, and monitoring of any adverse reactions. Demographics, clinical characteristics and drug efficacy were also compared between the two groups.

Results

Among the 60 initially enrolled patients (CP 30, AMC 30), 5 patients in the CP group and 6 in the AMC group were excluded due to poor compliance. There were no significant differences in demographic data including age, sex, initial signs and symptoms, endoscopic and X-ray findings between the two groups. Rates of improvement after 2 weeks were 96% and 95.8% in the CP and AMC group, respectively. Sinus symptoms were changed significantly after 2 and 4 weeks, however, there was no difference between groups (P=0.41). The most common adverse reaction was gastrointestinal complication, diarrhea occurred in 1 patient in the CP group and 6 in the AMC group (P=0.04).

Conclusion

CP and AMC were both effective in treating ARS. The difference of treatment outcome was not found between the two groups, however, gastrointestinal complications were less prevalent in the CP group.