Larrey D, Amouyal G, Pessayre D, Degott C, Danne O, Machayekhi J P, Feldmann G, Benhamou J P
Unité de Recherches de Physiopathologie Hépatique, INSERM U24, Hôpital Beaujon, Clichy, France.
Gastroenterology. 1988 Jan;94(1):200-3. doi: 10.1016/0016-5085(88)90631-2.
We report the case of a patient in whom amitriptyline administration for 5 wk was followed by prolonged cholestasis. Jaundice and pruritus lasted 19 and 20 mo, respectively. Three liver biopsies were performed at different stages of the disease showing the course of liver lesions. Cholestasis initially located in the region of the hepatic venule came to be associated with the progressive development of portal tract lesions consisting of inflammatory infiltration, fibrosis, and disappearance of interlobular bile ducts. Amitriptyline hydroxylation and dextromethorphan O-demethylation are deficient in subjects with the poor metabolizer phenotype of debrisoquine. Drug oxidation phenotyping with dextromethorphan showed that this patient had the extensive metabolizer phenotype. This observation demonstrates that amitriptyline can induce prolonged cholestasis and suggests that the susceptibility to develop liver injury while taking this drug may not be related to a genetic deficiency of its hydroxylation.
我们报告了一例患者，其服用阿米替林5周后出现了长期胆汁淤积。黄疸和瘙痒分别持续了19个月和20个月。在疾病的不同阶段进行了三次肝活检，显示了肝脏病变的过程。胆汁淤积最初位于肝小静脉区域，后来与门管区病变的逐渐发展相关，门管区病变包括炎症浸润、纤维化和小叶间胆管消失。去甲丙咪嗪代谢不良表型的受试者中，阿米替林羟化和右美沙芬O-去甲基化功能不足。用右美沙芬进行药物氧化表型分析表明，该患者具有广泛代谢者表型。这一观察结果表明，阿米替林可诱发长期胆汁淤积，并提示服用该药时发生肝损伤的易感性可能与其羟化的遗传缺陷无关。
