Utili R, Adinolfi L E, Tripodi M F
Istituto Terapia Medica, II Università di Napoli, Italy.
Ital J Gastroenterol. 1995 Jul-Aug;27(6):332-4.
The therapeutic index of either taurocholate (TC) or tauroursodeoxycholate (TUDC) administration in the treatment of drug-induced cholestasis was evaluated in perfused rat liver using a dose-response study. During estradiol-17-beta-glucuronide cholestasis, TC was more effective than TUDC in ameliorating bile flow but showed a low margin of safety since high doses caused additional toxicity. In contrast, TUDC ameliorated cholestasis even at very high doses with no adverse effects. In the model of chlorpromazine cholestasis, TC infusion did not correct but rather aggravated cholestasis, whereas TUDC at nonsaturating doses reversed the cholestasis and only at very high doses caused some toxicity. TUDC shows a good therapeutic index and may be employed with a reasonable margin of safety in the treatment of drug cholestasis.
使用剂量反应研究，在灌注大鼠肝脏中评估了牛磺胆酸盐（TC）或牛磺熊去氧胆酸盐（TUDC）给药治疗药物性胆汁淤积的治疗指数。在雌二醇 - 17 - β - 葡萄糖醛酸酯引起的胆汁淤积期间，TC在改善胆汁流量方面比TUDC更有效，但由于高剂量会导致额外毒性，其安全边际较低。相比之下，即使在非常高的剂量下，TUDC也能改善胆汁淤积且无不良反应。在氯丙嗪胆汁淤积模型中，输注TC不能纠正反而加重胆汁淤积，而在非饱和剂量下，TUDC可逆转胆汁淤积，只有在非常高的剂量下才会引起一些毒性。TUDC显示出良好的治疗指数，在治疗药物性胆汁淤积时可在合理的安全边际内使用。
