Lovisetto P, Giorcelli W, Actis G C, Biarese V
Minerva Med. 1977 Jan 14;68(2):73-81.
The value of phenobarbital in the treatment of free bilirubin icterus is demonstrated by a series of clinical experiments in which the drug was administered to patients with bilirubinaemia, even at high levels, the situation being brought back to normal within about two weeks. The percentage excreted with the urine in a conjugated form of various drugs proved higher in subjects treated with phenobarbital than in controls, thus proving that the drug acts as an enzymic inductor. Moreover it is ineffective in patients genetically lacking in the capacity to synthesize glycuronyltransferase. The induction of this latter enzyme, however, does not exhaust the effects of the barbiturate for it has been shown that phenobarbital is capable of speeding up the disappearance of exogenous bilirubin from the plasma in animals, of stimulating bile flow and increasing uptake of the pigment by the liver. The increase in bile flow is of the order of 30% and takes place by way of a modification in the flow fraction independent of bile salts. It would also appear that the drug is capable of increasing the activity of 7-alpha-hydroxylase, an enzyme that represents the rate limiting step in the synthesis of biliary salts. Other drugs commonly used in the treatment of free bilirubin icterus such as ethanol, rifampicin and uridindiphosphoglucose are considered. Finally the case of a female patient who from birth had presented persistent free bilirubin icterus of about 8 mg% is reported. After 14 days treatment with phenobarbital (100 mg X 2) blood levels of the pigment had returned to normal.
一系列临床实验证明了苯巴比妥在治疗游离胆红素黄疸中的价值。在这些实验中,该药物被施用于患有胆红素血症的患者,即便胆红素水平很高,大约两周内情况就能恢复正常。与对照组相比,接受苯巴比妥治疗的受试者中,以结合形式经尿液排泄的各种药物的百分比更高,从而证明该药物具有酶诱导剂的作用。此外,它对那些基因上缺乏合成葡萄糖醛酸转移酶能力的患者无效。然而,后一种酶的诱导并没有穷尽巴比妥酸盐的作用,因为已经表明苯巴比妥能够加速动物血浆中外源性胆红素的消失,刺激胆汁流动并增加肝脏对色素的摄取。胆汁流量增加约30%,是通过与胆盐无关的流量分数的改变实现的。似乎该药物还能够增加7-α-羟化酶的活性,该酶是胆盐合成中的限速步骤。文中还考虑了其他常用于治疗游离胆红素黄疸的药物,如乙醇、利福平和尿苷二磷酸葡萄糖。最后报告了一名女性患者的病例,该患者自出生以来一直存在约8mg%的持续性游离胆红素黄疸。在用苯巴比妥(100mg×2)治疗14天后,色素的血液水平恢复正常。