van de Meeberg P C, Wolfhagen F H, Van Berge-Henegouwen G P, Salemans J M, Tangerman A, van Buuren H R, van Hattum J, van Erpecum K J
University Hospital Utrecht, Department of Gastroenterology, The Netherlands.
J Hepatol. 1996 Dec;25(6):887-94. doi: 10.1016/s0168-8278(96)80293-5.
Ursodeoxycholic acid (UDCA) improves liver biochemistry in primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC). Since UDCA acts partly by reducing the intestinal absorption of hydrophobic endogenous bile salts and is poorly absorbed from the intestine, a multiple dose regimen has been advocated. Single dose treatment, on the other hand, may improve compliance.
The effects of a single or multiple dose regimen on liver enzymes and serum and biliary bile salts composition were evaluated.
Twenty-seven patients (19 PSC, 8 PBC), most with early stage disease, received UDCA (10 mg kg-1 day-1) in a single dose at bed time (n = 13) or in three divided gifts with meals (n = 14) over 3 months. Five patients had both treatment regimens in random order with a 1-month wash-out period in between.
Liver biochemistry equally improved in both groups. Biliary enrichment (% UDCA of total bile salts, mean +/- SEM) was 40.1 +/- 2.4 in the single dose group vs 40.8 +/- 2.8 in the multiple dose group (p = NS) and was positively correlated with biochemical improvement (AP: r = 0.47, p = 0.02; GGT: r = 0.58, p = 0.002; ASAT: r = 0.67, p = 0.002; ALAT: r = 0.52, p = 0.01). Biochemical improvement was not correlated with the concentration or %UDCA in serum. Patients participating in the cross-over design had comparable biochemical response and biliary %UDCA during both regimens.
Single and multiple dose UDCA have similar effects on liver biochemistry and biliary enrichment in cholestatic liver disease. Biochemical improvement appears to be related to biliary (but not serum) enrichment with UDCA.
熊去氧胆酸（UDCA）可改善原发性胆汁性肝硬化（PBC）和原发性硬化性胆管炎（PSC）患者的肝脏生化指标。由于UDCA部分作用是通过减少肠道对疏水性内源性胆汁盐的吸收，且其在肠道的吸收较差，因此一直主张采用多剂量给药方案。另一方面，单剂量治疗可能会提高依从性。
评估单剂量或多剂量给药方案对肝酶以及血清和胆汁胆汁盐成分的影响。
27例患者（19例PSC，8例PBC），大多数处于疾病早期，在3个月内接受UDCA（10 mg·kg⁻¹·d⁻¹）治疗，其中13例在睡前单剂量给药，14例分三次随餐给药。5例患者以随机顺序接受两种治疗方案，中间有1个月的洗脱期。
两组患者的肝脏生化指标均有同等程度改善。单剂量组胆汁中UDCA富集率（占总胆汁盐的百分比，均值±标准误）为40.1±2.4，多剂量组为40.8±2.8（p=无显著性差异），且与生化指标改善呈正相关（碱性磷酸酶：r=0.47，p=0.02；γ-谷氨酰转移酶：r=0.58，p=0.002；天冬氨酸转氨酶：r=0.67，p=0.002；丙氨酸转氨酶：r=0.52，p=0.01）。生化指标改善与血清中UDCA浓度或百分比无关。参与交叉设计的患者在两种治疗方案期间的生化反应和胆汁中UDCA百分比相当。
单剂量和多剂量UDCA对胆汁淤积性肝病的肝脏生化指标和胆汁富集有相似影响。生化指标改善似乎与胆汁中（而非血清中）UDCA富集有关。
