Simon B, Bergdolt H, Dammann H G, Müller P
Kreiskrankenhaus Schwetzingen.
Arzneimittelforschung. 1992 Feb;42(2):133-5.
In recent years there have been some reports of tolerance occurring in man with the antisecretory effect of H2 antagonists. We, therefore, studied the effect of 300 mg and 600 mg ranitidine (CAS 66357-35-5) daily and increasing i.v. doses of pentagastrin (0.37 microgram/kg, 0.75 microgram/kg, and 1.5 micrograms/kg body weight) on gastric acid output (mmol HCl/30 min) in 9 healthy volunteers. The study design was double-blind, randomized and cross-over. Pentagastrin stimulation was performed on day 1, day 8, and day 16. Increasing i.v. doses of pentagastrin induced an almost identical enhancement of volume secretion, total acid output as well as titratable acidity on the 3 study days. A 16-days treatment period with 300 mg and 600 mg ranitidine led to 80% and 90% inhibition of pentagastrin stimulated acid output. The degree of inhibition evoked by 300 mg and 600 mg ranitidine against pentagastrin was not statistically different during the 16-days treatment period; i.e. no significant tolerance did occur within 16 days. Our data suggest that, in contrast to intragastric acidity measurements, no significant decline of inhibitory effectiveness of ranitidine against i.v. pentagastrin could be observed in healthy male volunteers.
近年来,有一些关于人体对H2拮抗剂抗分泌作用产生耐受性的报道。因此,我们研究了每天300毫克和600毫克雷尼替丁(CAS 66357-35-5)以及静脉注射递增剂量的五肽胃泌素(0.37微克/千克、0.75微克/千克和1.5微克/千克体重)对9名健康志愿者胃酸分泌量(毫摩尔盐酸/30分钟)的影响。研究设计为双盲、随机和交叉试验。在第1天、第8天和第16天进行五肽胃泌素刺激试验。在3个研究日中,静脉注射递增剂量的五肽胃泌素几乎能同等程度地增强胃液分泌量、总酸分泌量以及可滴定酸度。300毫克和600毫克雷尼替丁为期16天的治疗使五肽胃泌素刺激的胃酸分泌受到80%和90%的抑制。在16天的治疗期内,300毫克和600毫克雷尼替丁对五肽胃泌素的抑制程度在统计学上无差异;即在16天内未出现明显的耐受性。我们的数据表明,与胃内酸度测量结果不同,在健康男性志愿者中未观察到雷尼替丁对静脉注射五肽胃泌素的抑制效果有明显下降。