Feely J, Wilkinson G R, Wood A J
N Engl J Med. 1981 Mar 19;304(12):692-5. doi: 10.1056/NEJM198103193041202.
We studied the influence of cimetidine on liver blood flow in eight normal subjects. Cimetidine acutely reduced liver blood flow during fasting by almost 25 per cent, as measured by indocyanine green clearance. Chronic cimetidine therapy (300 mg four times daily for seven days) reduced the flow by 33 per cent, as measured over eight hours by calculating the relative disposition of oral and intravenous propranolol. In addition to reducing the clearance of intravenous propranolol by decreasing live blood flow, cimetidine also inhibited the metabolism of oral propranolol and thereby further reduced elimination. The reduction in clearance of oral propranolol correlated positively (r = 0.87, P less than 0.05) with the average steady-state concentration of plasma cimetidine, suggesting that the inhibition of drug metabolism by cimetidine is dose related. Pulse rates at rest were markedly lower after propranolol plus cimetidine than after propranolol alone. The reduction in liver blood flow produced by cimetidine has important therapeutic implications for patients with alterations in liver and gastrointestinal blood flow and when drugs are used whose hepatic elimination depends on liver blood flow.
我们研究了西咪替丁对8名正常受试者肝脏血流的影响。通过吲哚菁绿清除率测定，禁食期间西咪替丁可使肝脏血流急性减少近25%。慢性西咪替丁治疗（每日4次，每次300毫克，共7天）通过计算口服和静脉注射普萘洛尔的相对处置情况，在8小时内测定显示血流减少了33%。除了通过减少肝脏血流降低静脉注射普萘洛尔的清除率外，西咪替丁还抑制口服普萘洛尔的代谢，从而进一步减少其消除。口服普萘洛尔清除率的降低与血浆西咪替丁的平均稳态浓度呈正相关（r = 0.87，P < 0.05），表明西咪替丁对药物代谢的抑制作用与剂量相关。普萘洛尔加西咪替丁治疗后静息脉搏率明显低于单独使用普萘洛尔后。西咪替丁导致的肝脏血流减少对于肝脏和胃肠道血流改变的患者以及使用肝脏消除依赖于肝脏血流的药物时具有重要的治疗意义。
