Miescher G, Paumgartner G, Preisig R
Eur J Clin Invest. 1983 Dec;13(6):439-45. doi: 10.1111/j.1365-2362.1983.tb00126.x.
Portal-systemic spill-over of unconjugated ursodeoxycholic acid (UDCA) was assessed in ten healthy subjects, six patients with mild chronic liver disease and eight patients with cirrhosis. Following oral administration of UDCA (1.5 mg/kg body weight), serum concentrations of unconjugated UDCA were measured during 2 h using a capillary gas-liquid chromatographic method. Peak time of UDCA varied from 15 to 30 min, but was not significantly different in the three groups studied. Peak concentration was increased up to two-fold in patients with mild, and up to three-fold in patients with cirrhotic liver disease. Since, in addition, plasma disappearance rate (k) was markedly impaired in cirrhotics (1.7 +/- SD 0.5%/min, compared to 2.8 +/- 0.6 in healthy controls), the calculated area under the curve (AUC) was on the average five-fold that in controls. In two healthy and four cirrhotic subjects, the data obtained after oral administration were compared with those after i.v. loading with the same UDCA dose. The k-values after the two routes of administration were practically identical. Calculated systemic availability was 50% in normals, 78-87% in cirrhotics, 90 and 136% in two patients with surgical porta-caval shunt. It is concluded that the portal-systemic spill-over of UDCA in patients with liver disease is increased primarily due to portal-systemic shunting. Since in the normal liver hepatic extraction of conjugated, endogenous bile acids is greater than 80%, diminished first-pass elimination is expected to augment systemic concentrations even more, particularly when measured after a meal.
在10名健康受试者、6名轻度慢性肝病患者和8名肝硬化患者中评估了未结合型熊去氧胆酸（UDCA）的门体分流情况。口服UDCA（1.5mg/kg体重）后，采用毛细管气液色谱法在2小时内测定未结合型UDCA的血清浓度。UDCA的峰值时间在15至30分钟之间，但在所研究的三组中无显著差异。轻度患者的峰值浓度增加至两倍，肝硬化患者增加至三倍。此外，肝硬化患者的血浆清除率（k）明显受损（1.7±标准差0.5%/分钟，健康对照为2.8±0.6），因此计算出的曲线下面积（AUC）平均为对照组的五倍。在2名健康受试者和4名肝硬化受试者中，比较了口服给药后与静脉注射相同剂量UDCA后的结果。两种给药途径后的k值几乎相同。正常受试者的计算全身利用率为50%，肝硬化患者为78 - 87%，两名门腔静脉分流手术患者分别为90%和136%。结论是，肝病患者中UDCA的门体分流增加主要是由于门体分流。由于在正常肝脏中，结合型内源性胆汁酸的肝提取率大于80%，预计首过消除减少会进一步增加全身浓度，尤其是在餐后测量时。
