Angelin B, Einarsson K, Leijd B
Eur J Clin Invest. 1981 Jun;11(3):185-9. doi: 10.1111/j.1365-2362.1981.tb01839.x.
In order to determine whether the clofibrate-induced increase in bile cholesterol saturation is transitory, duodenal bile samples were analysed from sixteen hyperlipoproteinaemic patients before and after 6 months to 2 years treatment with clofibrate, 2 g daily. Standardized dietary and weight conditions were obtained. In all but two subjects cholesterol saturation remained elevated (150 +/- 7%, mean +/- SEM) compared to pretreatment values (112 +/- 6%, P less than 0.01). In nine of the patients, duodenal bile was obtained also after 6 weeks of treatment. Although two patients with increased saturation at 6 weeks displayed a return to basal values at 2 years, the majority showed no consistent changes between these two occasions. Addition of chenodeoxycholic acid to clofibrate medication led to a normalization of cholesterol saturation (from 145 +/- 9 to 89 +/- 18%, P less than 0.01) in eight out of nine patients studied. The serum levels of total cholesterol and triglycerides, very low density lipoprotein and high density lipoprotein cholesterol were not significantly changed. However, the low density lipoprotein (LDL) cholesterol concentration was increased by 15--20% (from 4.8 +/- 0.3 to 5.7 +/- 0.4 mmol/l, P less than 0.01). It is concluded that clofibrate induces changes in biliary lipid composition which are consistent over at least 2 years of treatment. Possible measures to avoid these effects must therefore also be taken over a prolonged time. Chenodeoxycholic acid prevents the lithogenic effect of clofibrate but it cannot presently be recommended as an adjunct to clofibrate treatment since it simultaneously causes a rise in the serum concentration of LDL-cholesterol.
为了确定氯贝丁酯引起的胆汁胆固醇饱和度升高是否是暂时的，对16名高脂血症患者在接受每日2克氯贝丁酯治疗6个月至2年之前和之后的十二指肠胆汁样本进行了分析。维持标准化饮食和体重条件。除两名受试者外，与治疗前值（112±6%）相比，其他所有受试者的胆固醇饱和度均保持升高（150±7%，均值±标准误，P<0.01）。其中9名患者在治疗6周后也采集了十二指肠胆汁。尽管有两名患者在6周时饱和度升高，但在2年时恢复到了基础值，但大多数患者在这两个时间点之间没有一致的变化。在氯贝丁酯治疗中添加鹅去氧胆酸，使所研究的9名患者中的8名胆固醇饱和度恢复正常（从145±9%降至89±18%，P<0.01）。血清总胆固醇、甘油三酯、极低密度脂蛋白和高密度脂蛋白胆固醇水平没有显著变化。然而，低密度脂蛋白（LDL）胆固醇浓度升高了15%-20%（从4.8±0.3毫摩尔/升升至5.7±0.4毫摩尔/升，P<0.01）。结论是，氯贝丁酯至少在2年的治疗期内会引起胆汁脂质成分的持续变化。因此，也必须在较长时间内采取可能的措施来避免这些影响。鹅去氧胆酸可预防氯贝丁酯的致石作用，但目前不能推荐将其作为氯贝丁酯治疗的辅助药物，因为它会同时导致血清LDL胆固醇浓度升高。
