Diarrhea associated with lansoprazole

Lansoprazole is a proton pump inhibitor widely prescribed for gastroesophageal reflux and benign peptic ulcer disease. According to the manufacturer's package insert (TAP Pharmaceuticals, Lake Forest, IL, USA), the most common side-effects are diarrhea, headache and abdominal pain, which occur in approximately 3% of patients and are reversible with drug discontinuation. An unusual case of microscopic colitis is reported in a previously asymptomatic patient who developed new-onset diarrhea after initiation of lansoprazole. The case is reviewed and possible mechanisms of diarrhea secondary to proton pump inhibitors are discussed.     

Measurement of postprandial changes in urine acid output to detect changes of gastric acid secretion after proton pump inhibitors in children

Acid inhibition after proton pump inhibitors in children is variable, and to measure it by a noninvasive method may help to tailor treatment. To study gastric acid inhibition after a single dose of PPI, by measuring urinary acid output (UAO), which decreases as parietal cells release acid into the stomach during a meal, we performed a prolonged pH monitoring in 31 children (age range 3–16 yrs). Esophageal and intragastric pH was recorded for 24 hr and for 5 more hr after a single dose of PPI or placebo. Urine was collected early in the morning, and 1 hr after a test meal. Intragastric and urinary parameters were analyzed for 5 hr after PPI and compared to the same 5 hr at baseline. After PPI, median gastric pH significantly increased, and median UAO became significantly smaller (–0.31 vs. –1.40 at baseline; P = 0.002) but was unchanged after placebo. Inhibition of gastric acid induced by PPI can be detected by changes in UAO and its determination may be useful to monitor the PPI effect.     

兰索拉唑对乙醇诱导大鼠胃黏膜损伤的保护作用及其机制

目的　研究兰索拉唑 (LP)对乙醇诱导大鼠胃黏膜损伤的保护作用 ,探讨胃泌素受体和环氧化酶 2 (COX 2 )表达在此过程中的作用。方法　大鼠ig给予LP 0 5、5、5 0mg·kg-1·d-1,或ig联合给予LP 5 0mg·kg-1·d-1和胃泌素受体拮抗剂AG 0 4 1R 3、10、30mg·kg-1·d-1,对照组ig给予羧甲基纤维素 (CMC) 2 5mg·kg-1·d-1,连续 14d。末次给药后 8h各组大鼠ig给予无水乙醇 1ml,观察胃损伤指数 (LI)及光镜下的胃黏膜病理学改变。酶免疫方法测定胃黏膜前列腺素E2 (PGE2 )水平 ,WesternBlot和免疫组化检测胃黏膜COX 2表达。评价特异性COX 2抑制剂NS 398对LP诱导的PGE2 合成及胃黏膜保护作用的影响。结果　在 0 5、5、5 0mg·kg-1LP组 ,LI分别为 (2 5 3± 0 33) %、(1 84±0 2 9) %和 (0 83± 0 12 ) % ,小于对照组 (3 6 5± 0 19) % (P<0 0 5 ) ;胃黏膜PGE2 含量分别为 (42 7± 32 ) ,(483± 12 1)和 (6 14± 82 ) pg·g-1wwt ,高于对照组 (2 6 6± 81) pg·g-1wwt(P <0 0 5 )。LP剂量依赖性地增加大鼠胃黏膜COX 2表达。然而 ,同时给予AG 0 4 1R阻断了LP诱导的胃黏膜保护作用、COX 2表达和PGE2 合成。NS 398抑制LP诱导的PGE2 合成及胃黏膜保护作用。结论　LP的胃黏膜保护作用与内源性胃泌素激活胃泌素受     

兰索拉唑、阿奇霉素和甲硝唑根除幽门螺杆菌的疗效-费用观察

目的 :观察兰索拉唑、阿奇霉素和甲硝唑短程低剂量三联疗法根除幽门螺杆菌 (Hp)的临床疗效和治疗费用。方法 :将 4 7例病人随机分为 2组 :治疗组 2 4例给兰索拉唑 30mg ,po ,qd× 1wk ,阿奇霉素 5 0 0mg ,po ,qd× 3d ,甲硝唑 4 0 0mg ,po ,bid× 3d。对照组 2 3例给奥美拉唑 2 0mg ,po ,bid× 1wk ,克拉霉素 5 0 0mg ,po ,bid× 1wk ,甲硝唑4 0 0mg ,po ,bid× 1wk。停药 1mo后采用14 C呼气试验复查Hp。结果 :治疗组和对照组Hp根除率分别为 92 %和 91% (P >0 .0 5 ) ;治疗费用为185 .84元和 6 2 3.96元 ;药物不良反应发生率 4 %和9% (P >0 .0 5 )。结论 :兰索拉唑、阿奇霉素和甲硝唑短程低剂量三联疗法根除Hp有较好效果 ,且治疗药品费用低 ,病人依从性好     

兰索拉唑脂质体的制备及性质考察

目的研究兰索拉唑阳离子脂质体的制备方法并考察其体外释放行为及稳定性等。方法采用正交设计筛选处方;采用乙醇注入法制备兰索拉唑脂质体;采用超滤法测定其包封率;采用透射电镜观察脂质体的外观形态;采用粒径分析仪和Zeta电位仪分别测定脂质体的粒径和Zeta电位;采用透析法考察脂质体的释放规律。结果制得的脂质体包封率约为(80±1.23)%(n=3);脂质体的形态为粒径均匀的球形和类球形;粒径为(184±21)nm(n=3),Zeta电位为(36.1±5)mV(n=3);脂质体的体外释放符合一级方程,具有较好的稳定性。结论优选得到的脂质体处方和制备工艺合理,制剂性质稳定,其体外释放具有缓释特点。     

注射用兰索拉唑在健康人体内单、多剂量的药动学研究

目的研究注射用兰索拉唑在中国健康人体内的单、多剂量药动学。方法24名健康志愿者随机分为3组,每组8人(男女各半),分别恒速静脉注射15、30、60 mg兰索拉唑进行单剂量药动学研究,30 mg剂量组继续给药,qd×7d,进行多剂量药动学研究。按试验方案采血,用高效液相色谱法测定血药浓度,DAS 2.0程序计算药动学参数。结果健康受试者单剂量给药15、30、60 mg兰索拉唑后主要的药动学参数分别为t_(max)(0.669±s 0.014)、(0.667±0.012)、(0.668±0.013)h;c_(max)(1.01±0.05)、(1.69±0.06)、(3.01±0.08)mg·L~(-1);AUC_(0～t)(3.8±0.3)、(6.5±0.3)、(10.26±0.24)mg·h·L~(-1);t_(1/2)(1.8±0.6)、(3.4±0.8)、(2.5±0.5)h。多剂量给药30 mg达稳态时,主要的药动学参数为t_(max)(0.668±0.011)h;c_(max)(1.74±0.05)mg·L~(-1);c_(min)(0.125±0.012)mg·L~(-1);AUC_(?)(6.5±0.3)mg·h·L~(-1);t_(1/2)(3.0±0.9)h;CL (3.8±0.4)L.h~(-1);c_(av)(0.271±0.014)mg·L~(-1);DF(6.0±0.4)%。结论兰索拉唑在连续多次给药后,体内无蓄积现象,血药浓度d4已达稳态。兰索拉唑剂量的增加与C_(max)、AUC_(0～1)和AUC_(0～∞)的增加呈正相关关系;兰索拉唑的体内过程在男女性别间无显著差异。     

“Proton-pump inhibitor-first” strategy versus “step-up” strategy for the acute treatment of reflux esophagitis: a cost-effectiveness analysis in Japan

Background Gastroesophageal reflux disease (GERD) is a common condition, and acid-suppressing agents are the mainstays of treatment. For the acute medical management of GERD, two different strategies can be proposed: either the most effective therapy, i.e., proton-pump inhibitors (PPIs), can be given first, or histamine H₂-receptor antagonists (H₂RAs) can be attempted first (the “step-up” approach). Methods A clinical decision analysis comparing the PPI-first strategy and the H₂RA-first “step-up” strategy for the acute treatment of reflux esophagitis in Japan was performed, using a Markov chain approach. Results The PPI-first strategy was consistently superior to the step-up strategy with regard to clinical outcomes for the patient and with regard to cost-effectiveness (direct cost per patient to achieve clinical success). This superiority was robust within the plausible range of probabilities according to the sensitivity analyses. Conclusions The PPI-first strategy is superior to the H₂RA-first “step-up” strategy with regard to both efficacy and cost-effectiveness and therefore, the PPI-first strategy is the preferred therapeutic approach for the acute medical treatment of reflux esophagitis.