Gonzalez-Martin G, Paulos C, Veloso B, Chesta J, Novoa X, Arancibia A
Int J Clin Pharmacol Ther Toxicol. 1987 Mar;25(3):139-42.
The effect of severe liver disease on ranitidine disposition was evaluated by comparing its kinetics in 5 healthy subjects and 11 patients with alcoholic cirrhosis. Cirrhotic patients had severe liver disease as evidenced by the presence of ascites, hepatic encephalopathy, jaundice, muscle wasting, and low serum albumin, but creatinine clearance did not differ significantly between controls and cirrhosis. Following intravenous administration of ranitidine, systemic clearance was decreased in cirrhosis. These decrease may be associated with changes in renal function, and decrease in hepatic metabolism, usually present in patients with severe hepatic failure. The distribution volume of ranitidine was also decreased in cirrhotics, but the difference between patients and controls was not significant. Biological half-life was significantly longer in cirrhotic patients than volunteers. This difference may be due to decrease in total body clearance found in cirrhotic patients. It is concluded that patients with severe liver cirrhosis could have elevated plasma level of ranitidine and that a reduction of ranitidine dosage is warranted in these patients.
通过比较雷尼替丁在5名健康受试者和11名酒精性肝硬化患者体内的动力学,评估了严重肝脏疾病对雷尼替丁处置的影响。肝硬化患者存在腹水、肝性脑病、黄疸、肌肉萎缩和低血清白蛋白,表明患有严重肝脏疾病,但对照组和肝硬化患者的肌酐清除率无显著差异。静脉注射雷尼替丁后,肝硬化患者的全身清除率降低。这些降低可能与肾功能变化以及严重肝功能衰竭患者通常存在的肝代谢降低有关。雷尼替丁的分布容积在肝硬化患者中也降低,但患者与对照组之间的差异不显著。肝硬化患者的生物半衰期明显长于志愿者。这种差异可能是由于肝硬化患者全身清除率降低所致。结论是,严重肝硬化患者的雷尼替丁血浆水平可能升高,这些患者有必要减少雷尼替丁剂量。