Bretagne J F, Reymann J M, Tassou J J, Allain H, Gosselin A, Gastard J
Gastroenterol Clin Biol. 1983 Apr;7(4):355-61.
The pharmacokinetics of 50 mg intravenous ranitidine and the consequences on pentagastrin (2 micrograms/kg/h)-stimulated gastric acid secretion were studied in ten cirrhotic patients. Group I (n = 5) included patients without ascite; group II (n = 5) was characterized by the presence of ascites. Blood creatinine was normal in all the subjects. In non-ascitic cirrhotic patients, pharmacokinetic parameters are similar to those published in healthy subjects. In group II ascitic cirrhotic patients, the half-life is significantly increased by 50 p. 100 (P less than 0.05), as compared to group I, due to a 38 p. 100 decrease of total clearance and to a 45 p. 100 decrease of renal clearance (P less than 0.05). Hepatic clearance and volume of distribution are similar in both groups. The percentage of the inhibition by ranitidine of pentagastrin-stimulated acid out-put, in 6 cirrhotic patients, is 95 +/- 4 p. 100 (SD) when measured at the maximal inhibition peak, and 71 +/- 4 p. 100 (SEM) on the average, during the 3 h following the injection. In conclusion, ranitidine may be considered as an effective anti-secretory drug in cirrhotic patients; the pharmacokinetic variations observed in ascitic cirrhotic patients are the result of the decrease of ranitidine renal clearance.
对10例肝硬化患者研究了静脉注射50毫克雷尼替丁的药代动力学及其对五肽胃泌素(2微克/千克/小时)刺激胃酸分泌的影响。第一组(n = 5)包括无腹水的患者;第二组(n = 5)的特征是有腹水。所有受试者的血肌酐均正常。在无腹水的肝硬化患者中,药代动力学参数与健康受试者中公布的参数相似。与第一组相比,在第二组腹水肝硬化患者中,半衰期显著增加50%(P<0.05),这是由于总清除率降低38%和肾清除率降低45%所致(P<0.05)。两组的肝清除率和分布容积相似。在6例肝硬化患者中,雷尼替丁对五肽胃泌素刺激的酸分泌的抑制百分比,在最大抑制峰值时为95±4%(标准差),注射后3小时内平均为71±4%(标准误)。总之,雷尼替丁可被认为是肝硬化患者有效的抗分泌药物;在腹水肝硬化患者中观察到的药代动力学变化是雷尼替丁肾清除率降低的结果。