毒理性
在多次临床试验中，使用chenodiol疗法溶解胆结石，高达30%的患者出现了血清转氨酶升高。这些升高通常在开始治疗后的2个月内出现，通常是轻微的、短暂的，并且不伴有症状或黄疸。在chenodiol治疗期间进行的肝脏活检通常显示轻度、非特异性变化。临床上明显的肝损伤伴黄疸并未报告。肝脏酶的升高通常是剂量相关的，通常在以较低剂量重新开始chenodiol治疗后不会复发。尽管在chenodiol治疗期间发生的血清酶异常引起了相当大的关注，但它们似乎相对良性。自从chenodiol获得批准并更广泛使用以来，至少有四例肝损伤伴黄疸的病例已经报告给了赞助商，但这些病例的临床特征和结果尚未发表。尽管如此，chenodiol的产品标签上有一个关于肝毒性的黑框警告，尽管它没有提供关于异常频率或如何应对的建议。因此，关于临床上明显的肝损伤与chenodiol治疗相关的报告的可靠性仍然不清楚。一旦发现ursodiol在较低剂量下与chenodiol同样有效，并且很少与血清酶升高相关，它就迅速取代了chenodiol，成为治疗胆结石的医疗疗法。
In multiple clinical trials of chenodiol therapy for dissolution of gallstones, serum aminotransferase elevations occurred in up to 30% of patients. The elevations generally arose within 2 months of starting therapy and were typically mild, transient and not accompanied by symptoms or jaundice. Liver biopsies done during chenodiol therapy generally showed mild, nonspecific changes. Clinically apparent liver injury with jaundice was not reported. The liver enzyme elevations were generally dose related and usually did not recur on restarting chenodiol at lower doses. While the serum enzyme abnormalities that occurred on chenodiol therapy generated considerable concern, they appeared to be relatively benign. Since the approval of chenodiol and its more widespread use, at least four instances of liver injury with jaundice have been reported to the sponsor, but the clinical features and outcomes of these cases have not been published. Nevertheless, the product label for chenodiol includes a boxed warning about hepatotoxicity although it does not provide advice on the frequency or how to respond to abnormalities. Thus, the reliability of reports of clinically apparent liver injury with chenodiol therapy remains unclear. Once ursodiol was found to be equally as effective as chenodiol, even at lower doses, and was rarely associated with serum enzyme elevations, it rapidly replaced chenodiol as medical therapy for gallstones.
来源:LiverTox
