Prichard P J, Jones D B, Yeomans N D, Mihaly G W, Smallwood R A, Louis W J
Br J Clin Pharmacol. 1986 Dec;22(6):663-8. doi: 10.1111/j.1365-2125.1986.tb02955.x.
To examine whether changes in inhibition of gastric acid secretion occur during chronic ranitidine therapy, duodenal ulcer patients in remission were studied before and after 9 months of maintenance ranitidine therapy (150 mg nocte). At each time, the effect of a bolus i.v. dose of ranitidine (50 mg) on pentagastrin-stimulated maximal acid output was measured. Oral and intravenous pharmacokinetic studies were also performed to examine whether changes in absorption or disposition occur during long-term dosage. After 9 months' therapy, ranitidine inhibited pentagastrin-stimulated secretion by a median of 62%, substantially less than the median inhibition of 95% pre-treatment. Median acid output in the period 60-120 min post-ranitidine was six times the pretreatment value. Since pharmacokinetic parameters were unaltered, this reduced ability to inhibit acid output appears to indicate reduced sensitivity of acid secreting mechanisms to ranitidine after prolonged dosage.
为了研究在长期雷尼替丁治疗期间胃酸分泌抑制是否发生变化，对处于缓解期的十二指肠溃疡患者在雷尼替丁维持治疗（150毫克，每晚一次）9个月前后进行了研究。每次均测量静脉推注雷尼替丁（50毫克）对五肽胃泌素刺激的最大酸分泌量的影响。还进行了口服和静脉药代动力学研究，以检查长期给药期间吸收或处置是否发生变化。治疗9个月后，雷尼替丁抑制五肽胃泌素刺激的分泌的中位数为62%，大大低于治疗前95%的中位数抑制率。雷尼替丁给药后60 - 120分钟期间的酸分泌量中位数是治疗前值的六倍。由于药代动力学参数未改变，这种抑制酸分泌的能力降低似乎表明长期给药后酸分泌机制对雷尼替丁的敏感性降低。
