A decade-long sour-taste sensation successfully treated with a proton-pump inhibitor

We report a case study of a 54-year-old Japanese woman who persistently suffered from a sour-taste sensation in her mouth for 10 years, and was treated with a proton-pump inhibitor (PPI). She found sour-tasting meals irritable, and after eating such meals the sour-taste sensation worsened. She also complained of eructation and regurgitation. Upper gastrointestinal (GI) endoscopy showed duodenal erosion, superficial gastritis, and erosive oesophagitis. After 2 weeks of PPI therapy (lansoprazole, 30 mg day(-1)) the sour taste subjectively decreased to 70%, and after 6 weeks the symptoms disappeared. In addition to increased sensitivity of the mouth, gastro-oesophageal reflux might have created her obstinate sour-taste sensations. It is suggested that in such cases PPI therapy should be attempted.     

兰索拉唑对Hp引起糜烂性胃炎患者Th1/Th2漂移的影响

目的：探讨口服兰索拉唑对Hp引起糜烂性胃炎患者Th1/Th2漂移的影响。方法将我科诊断为糜烂性胃炎的92例患者作为研究对象,分为两组。将46例合并Hp感染者为实验组,另外46例Hp阴性者设为对照组,两组均给予兰索拉唑肠溶胶囊;实验组加用克拉霉素及阿莫西林抗Hp治疗;治疗后检查Hp;检测并收集患者治疗前、后血清样本,应用ELISA方法检测IFN-γ、IL-4水平。结果治疗1月后两组患者Hp检测均为阴性;治疗前实验组IFN-γ、IL-4及IFN-γ/IL-4均显著低于对照组（P<0.05）;治疗后两组IFN-γ、IL-4及IFN-γ/IL-4差异均无统计学意义（P>0.05）。实验组与对照组总有效率分别为93.5%、82.6%,差异无统计学意义（P>0.05）。两组患者均无严重并发症发生。结论 Hp感染可致糜烂性胃炎患者血清IFN-γ、IL-4水平降低,Th1向Th2细胞漂移;兰索拉唑可逆转Hp致病患者血清IFN-γ、IL-4水平降低,逆转Th1向Th2细胞漂移效应。     

LC-MS/MS法同时测定人血浆中兰索拉唑与代谢产物的浓度及其药动学研究(英文)

目的建立同时测定人血浆中兰索拉唑及其代谢产物5’-羟基兰索拉唑和兰索拉唑砜的LC-MS/MS法。方法血浆样本用乙腈沉淀蛋白后,选用Zorbax SB-C18 Narrow-Bore色谱柱(150 mm×2.1 mm,5μm),以甲醇︰10 mmol.L-1乙酸铵(65︰35,V/V)为流动相,流速为0.4 mL.min-1。选用API3200型三重四极杆串联质谱仪的多重反应监测(MRM)扫描方式进行监测,电喷雾离子化源,负离子方式。结果兰索拉唑、5’-羟基兰索拉唑、兰索拉唑砜以及内标奥美拉唑的保留时间分别为2.63、1.56、2.21、2.30 min;血浆中兰索拉唑、5’-羟基兰索拉唑、兰索拉唑砜的线性范围分别为2.00～800、1.00～400、0.200～80.0μg.L-1(r>0.99),定量下限分别为2.00、1.00、0.200μg.L-1;日内、日间相对标准差(RSD)均小于8.0%;相对偏差(RE)均在±6.0%的范围以内;提取回收率较高,且可重现;兰索拉唑、5’-羟基兰索拉唑、兰索拉唑砜在各种贮存条件下均较稳定。该方法成功地应用于兰索拉唑肠溶片在中国健康人体内的药动学研究,兰索拉唑、5’-羟基兰索拉唑、兰索拉唑砜的ρmax分别为165～1400、15.8～177、10.2～530μg.L-1,AUC0-t分别为651～7 189、99.3～639、20.5～4 372μg.h.L-1。兰索拉唑及其代谢产物的药动学存在显著的个体间差异。结论该方法快速、灵敏、专属性强、重现性好,适用于兰索拉唑及其代谢产物的人体药动学研究。     

HPLC法测定兰索拉唑肠溶片的血药浓度

目的建立HPLC法测定兰索拉唑肠溶片的血药浓度。方法采用高效液相色谱法,色谱柱:Hypersil ODS(250 mm×4.6 mm,5μm),柱温:40℃,流动相为水∶乙腈∶正辛胺(620∶380∶1),流速:1.2 ml.min-1,检测波长:285 nm。结果兰索拉唑在0.05～2.00 mg.L-1范围内线性关系良好(r=0.999 8),平均回收率为99.48%,RSD=4.50%。结论该方法灵敏、准确、稳定,适用于兰索拉唑的血药浓度检测。     

注射用兰索拉唑在中国健康人体内的药动学

目的:研究注射用兰索拉唑在健康人体内的药动学特征。方法:30名健康受试者随机分为3组,男女各半,分别静脉滴注兰索拉唑15,30,60mg,进行低、中、高单剂量药动学研究。30mg剂量组并进行多剂量药动学研究。采用LC-MS/MS测定血浆中兰索拉唑的浓度。应用DAS2.1.1软件计算药动学参数。结果:30名健康受试者分别单次静脉滴注注射用兰索拉唑15,30,60mg的主要药动学参数如下tmax为(0.67±0.00),(0.67±0.00),(0.73±0.09)h;Cmax为(857.1±251.2),1 738.5±263.8),(3 609.4±421.6)μg.L-1;AUC0-12为(2 873.9±2 065.4),(3 366.2±1 138.9),(12 321.1±5 632.5)μg.h.L-1;t1/2为(2.5±1.8),(1.4±0.4),(3.0±1.8)h。多次给药的主要药动学参数如下tmax为(0.70±0.07)h;Cmax为(1 530.2±305.1)μg.L-1;AUC0-12为(3 048.1±1 181.0)μg.h.L-1;AUCSS为(3 048.1±1 181....     

甲硝唑对兰索拉唑在大鼠体内药动学的影响

目的:研究甲硝唑在大鼠体内对兰索拉唑药动学特征的影响。方法:通过对兰索拉唑及细胞色素P450酶2C19(CYP2C19)代谢产物5-羟基兰索拉唑和细胞色素P450酶3A4(CYP3A4)代谢产物兰索拉唑砜的血药浓度的测定,计算大鼠体内药动学参数,以甲硝唑联合兰索拉唑用药组与兰索拉唑单独用药组的AUC0-4h比值为指标,研究甲硝唑对大鼠体内兰索拉唑代谢的影响。结果:联用甲硝唑后,兰索拉唑的AUC0-4h降低为单独使用兰索拉唑组的(0.20±0.06)倍(P<0.05)。甲硝唑显著增加5-羟基兰索拉唑与兰索拉唑AUC0-4h的比值,从(0.24±0.08)增至(0.39±0.19)(P<0.05)。结论:甲硝唑在大鼠体内对兰索拉唑CYP3A4主导的磺化代谢抑制作用不明显,对CYP2C19主导的羟化代谢途径可能有诱导作用。     

兰索拉唑联合血凝酶治疗急性上消化道出血的疗效观察

目的:观察兰索拉唑联合血凝酶对急性上消化道出血的治疗效果。方法:将46例急性上消化道出血患者随机分为两组,治疗组24例,对照组22例。治疗组给予兰索拉唑30 mg加入生理盐水100 mL静脉滴注,每日2次,联合应用血凝酶1 KU静脉注射,每日1次。对照组给予法莫替丁20 mg加入生理盐水50 mL静脉滴注,每日2次,联合应用血凝酶1 KU静脉注射,每日1次。两组疗程均为5 d,观察两组止血效果。结果:治疗组止血总有效率(91.67%)高于对照组(63.63%),差异有统计学意义(P<0.05)。结论:兰索拉唑联合血凝酶治疗上消化道出血经济、有效,值得临床推广应用。     

HPLC-MS/MS测定大鼠肝微粒体孵育体系中兰索拉唑代谢产物浓度

目的 建立大鼠肝微粒体酶孵育系统中兰索拉唑代谢产物5-羟基兰索拉唑及兰索拉唑砜的检测方法,并对体外孵育条件进行优化。方法 采用HPLC-MS/MS测定微粒体酶孵育系统中代谢产物的浓度,用单因素法对各孵育条件进行优化,采用Lineweaver-Burk双倒数法研究CYP2C19及CYP3A4的酶促动力学。结果 5-羟基兰索拉唑、兰索拉唑砜分别在5.57~2 520、5.42~2 480 ng·mL内线性关系良好。体外酶孵育条件为：兰索拉唑10 μmol·L, 肝微粒体酶量0.16 mg,孵育时间为10 min。结论 本实验建立的HPLC-MS/MS的方法快捷、灵敏,适用于兰索拉唑两种代谢产物的测定。体外酶孵育条件的优化,同时也为研究其他多种经CYP2C19及CYP3A4代谢的药物对兰索拉唑的代谢影响及相互作用奠定了基础。     

The demographic characteristics and health-related quality of life in a large cohort of reflux esophagitis patients in Japan with reference to the effect of lansoprazole: the REQUEST study

Background  Patients with reflux esophagitis (RE) in Western countries have impaired health-related quality of life (HRQOL). However, few data are available concerning HRQOL in Asian patients with RE. Aim  To determine the demographic characteristics, HRQOL, and the impact of lansoprazole treatment in a large cohort of RE patients in Japan. Methods  Patients with RE were enrolled. Lansoprazole was administered for 8 weeks and HRQOL assessed using the SF-8 and a newly developed questionnaire for RE-specific HRQOL (RESQ) at baseline and after 4 and 8 weeks of treatment. Results  Among enrolled patients, 2320 patients with the Los Angeles classification grade A to D esophagitis at enrollment to the study were analyzed. A higher proportion of older women was observed (in the group of patients aged ≥60 years, 61.3% were women). Prevalence of obesity was 4.7%. At baseline, HRQOL scores of RE patients were well below the mean for the Japanese general population in all domains of the SF-8. After 8 weeks of treatment with lansoprazole, these scores significantly improved to the levels of the general population (P < 0.01). Scores of RESQ also significantly improved (P < 0.01). Conclusions  Demographically, RE patients in Japan differ from those in Western countries with an increased proportion in older women and lower prevalence of obesity. RE has a marked negative impact on HRQOL, which is significantly improved by treatment with lansoprazole.     

Effect of pirenzepine on gastric endocrine cell kinetics during lansoprazole administration

We studied the effect of pirenzepine on gastric secretion kinetics in rats in a hypochlorhydric state induced by lansoprazole, a proton pump inhib-itor. Pirenzepine was administered intramuscularly at a dosage of 20 mg/kg twice daily; and lansorprazole, subcutaneously at 50 mg/kg once daily, both every day for 4 weeks. After the 4-week treatment, serum gastrin and plasma somatostatin levels were determined by radioimmunoassay. In addition, gastrin cells, somatostatin cells, and enterochromaffin-like cells were immunostained and counted. Serum gastrin levels were elevated, and gastrin and enterochromaffin-like cell numbers increased in the group on lansoprazole alone, compared with these values in the control group (which received distilled water). In the group on the lansoprazole and pirenzepine combination, serum gastrin levels decreased, and gastrin and enterochromaffin-like cell numbers were significantly decreased, compared with the respective variables in the group on lansoprazole alone, while the number of somatostatin cells increased in the group on the combination. Plasma somatostatin levels did not vary significantly in any group. It was thus demonstrated that pirenzepine corrects the abnormal gastric secretion kinetics resulting from treatment with lansoprazole alone, such as hypergastrinemia and gastrin and enterochromaffin-like cell hyperplasia. Received Oct. 28, 1997; accepted Mar. 27, 1998