泮托拉唑治疗重症脑出血并发应激性消化道溃疡的疗效研究

目的探讨泮托拉唑治疗重症脑出血并发应激性消化道溃疡的临床疗效。方法将我院收治的60例重症脑出血并发应激性消化道溃疡的患者随机分为观察组和对照组,各30例。观察组给予泮托拉唑治疗,对照组给予雷尼替丁治疗,比较两组患者的治疗效果及不良反应。结果观察组患者的总有效率为100.00%,对照组患者的总有效率为73.33%,两组比较差异有统计学意义(P<0.05)。观察组不良反应8例,对照组不良反应12例,两组不良反应率比较,差异有统计学意义(P<0.05)。结论泮托拉唑治疗重症脑出血并发应激性消化道溃疡的临床疗效显著,不良反应少,值得临床推广应用。     

泮托拉唑在治疗非静脉曲张性上消化道出血中的疗效观察

目的观察泮托拉唑对非静脉曲张性上消化道出血的临床疗效。方法选择非静脉曲张性上消化道出血患者69例,随机分为两组,其中治疗组35例,对照组34例,治疗组使用泮托拉唑（泮立苏）80mg,对照组使用奥美拉唑（洛赛克）40mg,分别加入生理盐水100ml中静脉注射,每12 h 1次,观察止血效果。结果泮托拉唑治疗组显效28例,有效6例,无效1例,总有效率为97.14%,平均住院费用为（10943±2197）元。奥美拉唑对照组显效29例,有效4例,无效1例,总有效率为97.06%,平均住院费用为（12072±3083）元。两组疗效及平均住院费用比较均无显著性差异（P均〉0.05）。结论泮托拉唑能够有效治疗非静脉曲张性上消化道出血。     

注射用泮托拉唑钠与注射用头孢唑肟钠配伍稳定性考察

目的考察室温[（20±1）℃]下,注射用泮托拉唑钠与注射用头孢唑肟钠在0.9%氯化钠注射液中的配伍稳定性。方法将泮托拉唑钠与头孢唑肟钠配伍后,在0～6 h内观察配伍液的外观变化,测定pH值,采用反相高效液相色谱法-二极管阵列检测器同时测定泮托拉唑钠与头孢唑肟钠配伍后的含量变化。结果6 h内混合液外观无明显变化,pH值及含量变化明显。结论在室温[（20±1）℃]下6 h内,注射用泮托拉唑钠与注射用头孢唑肟钠在0.9%氯化钠注射液中配伍不稳定。     

Lack of pharmacodynamic and pharmacokinetic interaction between pantoprazole and phenprocoumon in man

Objective: Pantoprazole is a selective proton pump inhibitor characterized by a low potential to interact with the cytochrome P450 enzymes in man. Due to the clinical importance of an interaction with anticoagulants, this study was carried out to investigate the possible influence of pantoprazole on the pharmacodynamics and pharmacokinetics of phenprocoumon. Methods: Sixteen healthy male subjects were given individually adjusted doses of phenprocoumon to reduce prothrombin time ratio (Quick method) to about 30–40% of normal within the first 5–9 days and to maintain this level. The individual maintenance doses remained unaltered from day 9 on and were administered until day 15. Additionally, on study days 11–15, pantoprazole 40 mg was given per once daily. As a pharmacodynamic parameter, the prothrombin time ratio was determined on days 9 and 10 (reference value) and on days 14 and 15 (test value), and the ratio test/reference was evaluated according to equivalence criteria. Results: The equivalence ratio (test/reference) for prothrombin time ratio was 1.02 (90% confidence interval 0.95–1.09), thus fulfilling predetermined bioequivalence criteria (0.70–1.43). The pharmacokinetic characteristics AUC_0–24h and C_max of S(−)-and R(+)-phenprocoumon were also investigated using equivalence criteria. Equivalence ratios and confidence limits of AUC_0–24h and of C_max of S(−)-phenprocoumon (0.93, 0.87–1.00 for AUC_0–24h; 0.95, 0.88–1.03 for C_max) and of R(+)-phenprocoumon (0.89, 0.82–0.96; 0.9, 0.83–0.98) were within the accepted range of 0.8–1.25. Conclusion: Pantoprazole does not interact with the anticoagulant phenprocoumon on a pharmacodynamic or pharmacokinetic level. Concomitant treatment was well tolerated. Received: 26 January 1996/Accepted in revised form:22 May 1996     

泮托拉唑对应激性溃疡患者热休克蛋白70含量的影响

目的研究泮托拉唑对应激性溃疡患者热休克蛋白70含量的影响,为探明其预防应激性溃疡的新机制提供依据。方法将符合纳入标准的62例应激性溃疡患者随机分为观察组和对照组。两组患者出现应激性溃疡时即开始用药物治疗:观察组泮托拉唑40 mg静滴,2次/d,对照组法莫替丁40 mg静滴,2次/d。疗程为开始至胃液引流液转为淡黄色并巩固1周的时间。收集3个时间点(刚出现咖啡色引流物、运用抑酸剂1周、引流胃液转黄后1周)患者的静脉血液(分别定义为U0、U1、U2期)。同时选择无消化道应激性溃疡出血10例患者作为正常组,收集其静脉血作为正常对照(相当于U0期)。观察比较观察组及对照组患者U1、U2期及正常组HSP70的表达。比较观察组和对照组患者引流胃液转为淡黄色所需平均时间。结果观察组与对照组患者U0期HSP70含量明显高于正常组,U1期明显高于U0期(P<0.05),观察组患者U1期HSP70含量明显高于对照组(P<0.05),观察组和对照组U2期HSP70含量明显低于U1期(P<0.05),观察组患者U2期HSP70含量明显高于对照组(P<0.05)。观察组引流胃液转为淡黄色所需平均时间明显短于对照组,观察组患者应激性溃疡愈合速度明显快于对照组。结论泮托拉唑能提高应激性溃疡患者热休克蛋白70表达,促进溃疡愈合速度较法莫替丁迅速,泮托拉唑愈合溃疡机制之一可能与提高HSP70表达有关。     

Esophageal cell proliferation in gastroesophageal reflux disease： Clinical-morphological data before and after pantoprazole

AIM： To evaluate esophageal mucosal defense mechanisms at an epithelial level to establish if pantoprazole treatment can induce ultrastructural healing and improvement in the proliferation activity of the esophageal epithelium in gastroesophageal reflux disease （GERD）. METHODS： This was a single-blinded study for pH- monitoring, and histological, ultrastructural and MIB1 immunostaining evaluation. Fifty eight patients with GERD were enrolled and underwent 24 h pH-monitoring and endoscopy. Patients were treated for 12 and 24 mo with pantoprazole. Esophageal specimens were taken for histological and ultrastructural evaluation, before and after the treatment. RESULTS： With transmission electron microscopy, all patients with GERD showed ultrastructural signs of damage with dilation of intercellular spaces （DIS）. After 3 mo of therapy the mean DIS values showed a significant reduction and the mean MIB1-LI values of GERD showed an increase in cell proliferation. A further 3 mo of therapy significantly increased cell proliferation only in the erosive esophagitis （ERD） group. CONCLUSION： Three months of pantoprazole therapy induced ultrastructural healing of mucosal damage in 89% and 93% of ERD and non-erosion patients, respectively. Moreover, long-term pantoprazole treatment may be helpful in increasing the capability for esophageal cell proliferation in GERD, particularly in ERD patients.     

质子泵抑制剂提高人胃腺癌细胞化学治疗敏感性研究

目的 探讨质子泵抑制剂(PPI)泮托拉唑(PPZ)是否通过抑制空泡型质子泵来逆转细胞内外pH梯度,从而增加肿瘤细胞化学治疗敏感性,并探讨PPZ最佳预处理时间、剂量及机制.方法 免疫印迹及免疫荧光法比较PPZ处理前、后人胃低分化腺癌细胞株SGC7901空泡型质子泵的表达及胞内分布变化.用BCECF-AM荧光探针检测不同浓度PPZ作用不同时间对细胞内pH值的影响.用四甲基偶氮唑盐比色法和膜联蛋白V-异硫氰酸荧光素-碘化丙啶试剂盒检测化学治疗药物联合PPZ的细胞毒性和细胞凋亡变化.用阿霉素检测PPZ对细胞内药物蓄积和潴留量的影响.结果 10和100μg/ml PPZ作用24 h后,空泡型质子泵表达的相对吸光度值(1.19±0.03和0.70±0.03)明显低于空白对照组(1.53±0.05),而1μg/ml PPZ可促进其表达(2.29±0.06).在10μg/ml PPZ作用第6和12小时,可见其对空泡型质子泵表达的抑制作用(相对吸光度值分别为0.32±0.02和0.13±0.02),在作用24 h后可改变空泡型质子泵的细胞内分布.10和100 ttg/ml PPZ作用24 h可使细胞内pH值(7.44±0.09和7.31±0.06)明显低于空白对照组(7.51±0.05),10μg/ml及以上浓度的PPZ可逆转细胞内外pH梯度.PPZ预处理24 h后予化学药物治疗的细胞存活率(58.71%±1.18%)低于单用化学治疗药物(74.33%±1.77%,P<0.05),其总凋亡率(80.81%±1.16%)和早期凋亡率(77.52%±1.13%)显著高于单用化学治疗药物(26.42%±1.19%和23.18%±0.92%,P值均<0.01).20、50和100 μg/ml PPZ作用24 h后的阿霉素释放指数(0.164±0.013、0.162±0.015、0.152±0.012)低于空白对照组(0.277±0.011,P值均<0.01).结论 PPZ预处理可提高人胃腺癌细胞的化学治疗敏感性.     

泮托拉唑辅助治疗消化性溃疡的临床研究

目的对泮托拉唑治疗消化性溃疡的临床疗效进行观察研究。方法将126例消化性溃疡患者随机分为对照组和治疗组,在常规治疗的基础上,对照组采用西米替丁进行静脉滴注,治疗组采取泮托拉唑进行静脉滴注。结果对照组总有效率为96.9%,治疗组总有效率100%,治疗组总有效率明显优于对照组(P<0.05)。结论泮托拉唑对于消化性溃疡的治疗具有明显疗效,且具备不良反应小的特点,值得在临床医学中推广。     

HPLC法测定泮托拉唑钠肠溶胶囊的耐酸力

目的：建立测定泮托拉唑钠肠溶胶囊耐酸力的方法。方法：采用HPLC法,色谱柱为Hypersil ODS2C18（250×4.6mm,5μm）,流动相为磷酸盐缓冲液（取磷酸氢二钠1.12g与磷酸二氢钠0.18g,加水溶解并稀释至1000ml）-乙腈（70：30）,检测波长288nm,流速1.0ml/min。结果：泮托拉唑钠线性范围为8.16-81.56μg/ml（r^2=0.9993）,平均回收率为99.05%,RSD=0.46%（n=9）,三批样品耐酸力均大于95%。结论：所用方法简便快速,专属性强,灵敏度高,准确度好。     

泮托拉唑治疗老年急性上消化道出血经济学分析

目的对泮托拉唑与奥美拉唑在治疗老年急性上消化道出血中的成本-效果进行分析。方法选择272例患者进行回顾性调查,运用成本-效果分析对泮托拉唑与奥美拉唑治疗老年急性上消化道出血的疗效及成本进行比较和分析。结果泮托拉唑与奥美拉唑治疗老年急性上消化道出血的总有效率基本相同,分别为94.73%与95.83%,两组成本分别为576元与1431.5元,成本-效果比分别为6.08与14.94（P〈0.05）,两组成本-效果比有显著性差异。结论应用泮托拉唑治疗老年急性上消化道出血价格相对低廉,成本-效果比优于奥美拉唑。