Okolicsanyi L, Lirussi F, Strazzabosco M, Jemmolo R M, Orlando R, Nassuato G, Muraca M, Crepaldi G
Drugs. 1986 May;31(5):430-48. doi: 10.2165/00003495-198631050-00003.
Many drugs are eliminated via the hepatobiliary route, after biotransformation in the liver. Some of them may affect bile flow and/or the hepatic secretion of biliary lipids such as bile acids, cholesterol and phospholipids. Bile acids are the most potent agents which increase bile flow, especially unconjugated bile acids. Other drugs which increase bile flow include phenobarbitone (phenobarbital), theophylline, glucagon and insulin. In contrast, ethacrynic acid, amiloride, ouabain, oestrogens and chlorpromazine are among those agents which decrease bile flow. Biliary bile acid secretion is altered by a variety of drugs, including cheno- and ursodeoxycholic acids (CDCA and UCDA), the bile acid sequestrants cholestyramine and colestipol, and ethinyloestradiol. The composition of bile can also be altered by drug therapy. Thus, clofibrate increases biliary cholesterol secretion, and reduces bile acid concentrations, without altering biliary phospholipid concentrations. However, other clofibrate derivatives may produce changes of a different pattern, suggesting that the risk of developing gallstones may differ for each derivative. Nicotinic acid and d-thyroxine also increase biliary cholesterol saturation, while CDCA and UDCA reduce biliary cholesterol concentration. The potential consequences of drug-induced changes in bile flow and composition extend to the liver, the gallbladder and the intestine. If adverse effects are to be avoided, further study in this often overlooked area is required.
许多药物在肝脏进行生物转化后，通过肝胆途径被清除。其中一些药物可能会影响胆汁流动和/或胆汁脂质（如胆汁酸、胆固醇和磷脂）的肝脏分泌。胆汁酸是增加胆汁流动的最有效物质，尤其是未结合的胆汁酸。其他增加胆汁流动的药物包括苯巴比妥、茶碱、胰高血糖素和胰岛素。相比之下，依他尼酸、阿米洛利、哇巴因、雌激素和氯丙嗪是减少胆汁流动的药物。多种药物会改变胆汁酸的分泌，包括鹅去氧胆酸和熊去氧胆酸（CDCA和UCDA）、胆汁酸螯合剂考来烯胺和考来替泊以及乙炔雌二醇。药物治疗也会改变胆汁的成分。因此，氯贝丁酯会增加胆汁中胆固醇的分泌，并降低胆汁酸浓度，而不改变胆汁中磷脂的浓度。然而，其他氯贝丁酯衍生物可能会产生不同模式的变化，这表明每种衍生物形成胆结石的风险可能不同。烟酸和d-甲状腺素也会增加胆汁中胆固醇的饱和度，而CDCA和UDCA会降低胆汁中胆固醇的浓度。药物引起的胆汁流动和成分变化的潜在后果会延伸至肝脏、胆囊和肠道。若要避免不良反应，需要在这个经常被忽视的领域进行进一步研究。
