Thomson A B, Mahachai V, Bailey R J, Kirdeikis P, Zuk L, Marriage B, Simpson I, Jamali F
Department of Medicine, University of Alberta, Edmonton, Canada.
J Gastroenterol Hepatol. 1996 Dec;11(12):1171-6. doi: 10.1111/j.1440-1746.1996.tb01847.x.
The present study was performed in six asymptomatic patients with a history of resistant duodenal ulcers in whom 24 h intragastric pH, gastric juice pepsin and PGE2 concentrations, as well as serum gastrin concentrations, were measured. We wanted to compare the effects on these parameters of a single night time (q.h.s.) dose of nizatidine 300 mg (N1), nizatidine 300 mg b.i.d. (N2), ranitidine 300 mg q.h.s. (R1) or ranitidine 300 mg b.i.d. (R2) compared with placebo (P). During the night (22.00-08.00 h), all treatments gave a higher mean pH than P, but during the day (08.00-22.00 h) the mean pH was higher than P only for patients administered R2 and N2. Doubling the dose of nizatidine (N2 vs N1) or ranitidine (R2 vs R1) increased the mean daytime pH, but had no effect on night time pH. The daytime pepsin concentration was unaffected by H2-receptor antagonists, while night time pepsin was lower with R1 and R2, but not with N1 or N2. The night time gastrin concentration was unaffected by H2-receptor antagonists; doubling the dose of the H2-receptor antagonist (R2 vs R1 and N2 vs N1) increased daytime gastrin concentration. During the night, each treatment increased PGE2 concentration by at least six-fold compared with P. Thus, where it is therapeutically indicated to achieve greater suppression of acid secretion, doubling the total daily dose by dosing with twice daily versus once daily night time nizatidine or ranitidine is efficacious.
本研究对6例有难治性十二指肠溃疡病史的无症状患者进行,测定了他们24小时胃内pH值、胃液胃蛋白酶和前列腺素E2(PGE2)浓度以及血清胃泌素浓度。我们想比较单次夜间(每晚一次)服用300毫克尼扎替丁(N1)、300毫克尼扎替丁每日两次(N2)、300毫克雷尼替丁每晚一次(R1)或300毫克雷尼替丁每日两次(R2)与安慰剂(P)对这些参数的影响。夜间(22:00 - 08:00时),所有治疗组的平均pH值均高于安慰剂组,但白天(08:00 - 22:00时),仅接受R2和N2治疗的患者平均pH值高于安慰剂组。将尼扎替丁(N2与N1相比)或雷尼替丁(R2与R1相比)的剂量加倍可提高白天的平均pH值,但对夜间pH值无影响。白天胃蛋白酶浓度不受H2受体拮抗剂影响,而夜间R1和R2组的胃蛋白酶浓度较低,但N1和N2组不受影响。夜间胃泌素浓度不受H2受体拮抗剂影响;将H2受体拮抗剂的剂量加倍(R2与R1以及N2与N1相比)可提高白天胃泌素浓度。夜间,与安慰剂相比,每种治疗均使PGE2浓度至少增加六倍。因此,在治疗上需要更大程度抑制胃酸分泌时,将尼扎替丁或雷尼替丁的每日总剂量加倍,即每日两次给药而非每晚一次给药是有效的。