兰索拉唑对胃酸分泌抑制作用的剂量-反应关系。
Dose-response relationship of lansoprazole to gastric acid antisecretory effects.
作者信息
Blum R A, Hunt R H, Kidd S L, Shi H, Jennings D E, Greski-Rose P A
机构信息
Clinical Pharmacokinetics Laboratory, Millard Fillmore Hospital, Buffalo, New York 14209, USA.
出版信息
Aliment Pharmacol Ther. 1998 Apr;12(4):321-7. doi: 10.1046/j.1365-2036.1998.00306.x.
BACKGROUND
Proton pump inhibitors have been found to be effective in numerous studies in patients with peptic ulcer disease, particularly associated with Helicobacter pylori and gastro-oesophogeal reflux disorders. Optimal healing rates of antisecretory therapy for peptic acid disease is dependent upon the degree and duration of acid suppression and the length of treatment.
OBJECTIVE
To evaluate the extent and duration of gastric acid suppression of several lansoprazole regimens, administered for 5 consecutive days in 32 healthy adult male subjects.
METHODS
Intragastric 24-h pH monitoring was performed in 32 healthy subjects in a randomized, double-blind, four-way crossover study. Sixteen subjects (Group 1) received lansoprazole 30 mg o.d. (once daily), 15 mg b.d. (twice daily), 30 mg b.d. and 30 mg t.d.s. (three times a day) for 5 days; and 16 subjects (Group 2) received lansoprazole 30 mg o.d., 60 mg o.d., 60 mg b.d. and 60 mg t.d.s. for 5 days.
RESULTS
Mean 24-h intragastric pH values for lansoprazole 30 mg o.d., 15 mg b.d., 30 mg b.d. and 30 mg t.d.s. were 4.47, 4.57, 5.07 and 5.63, respectively. Multiple-dose regimens of lansoprazole 30 mg b.d. and t.d.s. produced greater acid suppression compared to lansoprazole 30 mg o.d. and 15 mg b.d. There was no significant difference in acid suppression between lansoprazole 30 mg o.d. and 15 mg b.d. Mean 24-h intragastric pH values for lansoprazole 30 mg o.d., 60 mg o.d., 60 mg b.d. and 60 mg t.d.s. were 4.13, 4.45, 5.19 and 5.13, respectively. Multiple-dose regimens of lansoprazole 60 mg b.d. and t.d.s. produced significantly greater acid suppression compared to lansoprazole 30 mg o.d. and 60 mg o.d. There was no significant difference in acid suppression between lansoprazole 30 mg o.d. and 60 mg o.d. Lansoprazole 30 mg t.d.s., 60 mg b.d. and 60 mg t.d.s. produced significantly greater percentage time above pH 3, 4, 5 and 6 than did lansoprazole 30 mg o.d. Post-regimen serum gastrin values increased by 50-130% from pre-study mean values but remained within normal range and returned to pre-study values 7-14 days post-dosing.
CONCLUSIONS
Multiple-dose regimens of lansoprazole (> or =30 mg b.d. for 5 days) produce significantly increased intragastric pH and significantly longer duration of increased intragastric pH than does lansoprazole 30 mg administered once daily.
背景
质子泵抑制剂在众多针对消化性溃疡疾病患者的研究中已被证实有效，尤其适用于与幽门螺杆菌及胃食管反流疾病相关的情况。抗分泌疗法对胃酸相关疾病的最佳愈合率取决于胃酸抑制的程度、持续时间以及治疗时长。
目的
评估32名健康成年男性受试者连续5天服用几种兰索拉唑方案后胃酸抑制的程度和持续时间。
方法
在一项随机、双盲、四交叉研究中，对32名健康受试者进行24小时胃内pH监测。16名受试者（第1组）分别接受兰索拉唑30毫克每日一次、15毫克每日两次、30毫克每日两次以及30毫克每日三次，持续5天；另外16名受试者（第2组）分别接受兰索拉唑30毫克每日一次、60毫克每日一次、60毫克每日两次以及60毫克每日三次，持续5天。
结果
兰索拉唑30毫克每日一次、15毫克每日两次、30毫克每日两次以及30毫克每日三次的24小时平均胃内pH值分别为4.47、4.57、5.07和5.63。与兰索拉唑30毫克每日一次和15毫克每日两次相比，兰索拉唑30毫克每日两次和每日三次的多剂量方案产生了更强的胃酸抑制作用。兰索拉唑30毫克每日一次和15毫克每日两次在胃酸抑制方面无显著差异。兰索拉唑30毫克每日一次、60毫克每日一次、60毫克每日两次以及60毫克每日三次的24小时平均胃内pH值分别为4.13、4.45、5.19和5.13。与兰索拉唑30毫克每日一次和60毫克每日一次相比，兰索拉唑60毫克每日两次和每日三次的多剂量方案产生了显著更强的胃酸抑制作用。兰索拉唑30毫克每日一次和60毫克每日一次在胃酸抑制方面无显著差异。兰索拉唑30毫克每日三次、60毫克每日两次和60毫克每日三次在pH值高于3、4、5和6的时间百分比方面显著高于兰索拉唑30毫克每日一次。给药后血清胃泌素值较研究前平均值增加了50 - 130%，但仍在正常范围内，并在给药后7 - 14天恢复到研究前值。
结论
兰索拉唑多剂量方案（≥30毫克每日两次，持续5天）与每日一次服用30毫克兰索拉唑相比，可显著提高胃内pH值，并显著延长胃内pH值升高的持续时间。
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