Ohnishi K
First Department of Medicine, Chiba University School of Medicine, Japan.
Hepatogastroenterology. 1990 Jul;37 Suppl 1:6-10.
The effects of hepatic disease on the pharmacokinetics of the histamine H2-receptor antagonist famotidine were studied in seven healthy volunteers and 20 patients with chronic liver disease. The acute effects of famotidine on hepatic hemodynamics were studied in six healthy volunteers and eight patients with chronic liver disease, and its long-term effects on peptic ulcer, portal blood flow, and hepatic function were studied in 34 patients with chronic liver disease and peptic ulcer. Famotidine clearance was reduced only in patients with decompensated cirrhosis, probably because of concomitant renal impairment. Infusion of 20 mg of famotidine did not reduce hepatic or portal blood flow in healthy subjects, nor did it reduce the gradient between wedged hepatic vein pressure and free hepatic vein pressure or hepatic and portal blood flow in patients with chronic liver disease. An oral dose of 20 mg of famotidine twice daily for two months healed the peptic ulcers in 33 of 34 patients (97%) with chronic liver disease without altering portal blood flow and hepatic function. Even in patients with decompensated cirrhosis, famotidine did not change hepatic function. Thus, famotidine had no effect on hepatic hemodynamics or function in healthy subjects and patients with chronic liver disease. The drug was shown to be well tolerated and effective in the treatment of gastric and duodenal ulcer associated with chronic liver disease.
在7名健康志愿者和20名慢性肝病患者中研究了肝病对组胺H2受体拮抗剂法莫替丁药代动力学的影响。在6名健康志愿者和8名慢性肝病患者中研究了法莫替丁对肝血流动力学的急性影响,并在34名慢性肝病合并消化性溃疡的患者中研究了其对消化性溃疡、门静脉血流和肝功能的长期影响。仅失代偿期肝硬化患者的法莫替丁清除率降低,可能是由于合并肾功能损害。静脉输注20mg法莫替丁对健康受试者的肝或门静脉血流无影响,对慢性肝病患者的肝静脉楔压与游离肝静脉压之间的梯度或肝和门静脉血流也无影响。34例慢性肝病患者中,33例(97%)每日口服20mg法莫替丁两次,持续两个月,消化性溃疡愈合,且门静脉血流和肝功能未改变。即使在失代偿期肝硬化患者中,法莫替丁也不改变肝功能。因此,法莫替丁对健康受试者和慢性肝病患者的肝血流动力学或功能无影响。该药物在治疗与慢性肝病相关的胃和十二指肠溃疡方面耐受性良好且有效。