Sogni P, Hadengue A, Moreau R, Le Moine O, Soupison T, Oberti F, Farinotti R, Lebrec D
Unité de Recherches de Physiopathologie Hépatique (INSERM U-24), Hôpital Beaujon, Clichy, France.
J Hepatol. 1997 Mar;26(3):628-33. doi: 10.1016/s0168-8278(97)80429-1.
BACKGROUND/AIMS: The antithyroid drug propylthiouracil has been suggested for the treatment of alcoholic liver disease. Its beneficial effects could be due to either a decrease in hepatic oxygen consumption or an increase in hepatic blood flow. The aim of this study was to test these two hypotheses in patients with proven alcoholic cirrhosis.
The pharmacokinetic parameters after intravenous administration of 300 mg of propylthiouracyl were first determined in four patients. Then, the effects on systemic and splanchnic hemodynamics, and oxygen content were measured 45 and 90 min after the intravenous administration of 300 mg (n=6) or 600 mg (n=6) of propylthiouracil.
Systemic hemodynamics (heart rate, arterial pressure, cardiac output and systemic vascular resistance) and splanchnic hemodynamics (hepatic venous pressure gradient, hepatic and azygos blood flows) were not modified 45 and 90 min after the administration of 300 mg or 600 mg of propylthiouracil. Moreover, neither oxygen content in the radial artery, pulmonary artery or hepatic vein, nor systemic oxygen uptake was modified after propylthiouracyl administration. The absence of effect of propylthiouracyl administration was also confirmed in patients with cirrhosis with proven acute alcoholic hepatitis (n=7).
In patients with alcoholic cirrhosis, acute administration of propylthiouracyl has no effect on systemic and splanchnic hemodynamics or on oxygen contents. The presence of acute alcoholic hepatitis does not modify these results.
背景/目的:抗甲状腺药物丙硫氧嘧啶已被建议用于治疗酒精性肝病。其有益作用可能归因于肝脏氧消耗的减少或肝血流量的增加。本研究的目的是在确诊为酒精性肝硬化的患者中验证这两种假设。
首先在4例患者中测定静脉注射300mg丙硫氧嘧啶后的药代动力学参数。然后,在静脉注射300mg(n = 6)或600mg(n = 6)丙硫氧嘧啶后45分钟和90分钟测量其对全身和内脏血流动力学以及氧含量的影响。
静脉注射300mg或600mg丙硫氧嘧啶后45分钟和90分钟,全身血流动力学(心率、动脉压、心输出量和全身血管阻力)和内脏血流动力学(肝静脉压力梯度、肝和奇静脉血流量)未发生改变。此外,丙硫氧嘧啶给药后,桡动脉、肺动脉或肝静脉中的氧含量以及全身氧摄取均未改变。在确诊为急性酒精性肝炎的肝硬化患者(n = 7)中也证实了丙硫氧嘧啶给药无效。
在酒精性肝硬化患者中,急性给予丙硫氧嘧啶对全身和内脏血流动力学或氧含量无影响。急性酒精性肝炎的存在并未改变这些结果。