Milkiewicz P, Baiocchi L, Mills C O, Ahmed M, Khalaf H, Keogh A, Baker J, Elias E
Liver and Hepatobiliary Unit, Queen Elizabeth Hospital, Birmingham, UK.
J Hepatol. 1997 Dec;27(6):1106-9. doi: 10.1016/s0168-8278(97)80155-9.
BACKGROUND/AIMS: Cholyl-lysyl-fluorescein is a fluorescent analogue of the natural bile acid, cholyl glycine. In vivo and in vitro studies showed that this analogue has many biological characteristics similar to cholyl glycine. In this study we analysed cholyl-lysyl-fluorescein plasma clearance in six healthy volunteers as a potential quantitative liver function test.
The compound in water for injection was administered as an i.v. bolus in the dose of 0.02 mg/kg b.w.
The plasma elimination curve showed rapid, intermediate and slow phases of clearance. Half-life (T1/2 time) for the first (t1/2 1st phase), second (t1/2 2nd phase) and third (t1/2 3rd phase) phases of elimination was 1.7+/-0.9 min, 6.7+/-1.6 min and 68+/-17 min, respectively. Ninety-minute plasma retention (% dose/l plasma) was 2.2%. Cholyl-lysyl-fluorescein volume of distribution and residual fluorescence after 60 min were similar to the data obtained by others for natural or radiolabelled bile acids. In five out of six healthy volunteers a 25-fold higher dose of cholyl-lysyl-fluorescein (0.5 mg/kg b.w.) was injected to estimate the safety margins of the compound. This dose was eliminated at a disappearance rate similar to that of the dose of 0.02 mg/kg b.w. and did not cause any adverse reactions. Serum liver tests measured before and after injection did not change significantly.
This study showed that cholyl-lysyl-fluorescein clearance is similar to the clearance of endogenous natural bile acids and may potentially offer a new, dynamic test of liver function.
背景/目的：胆酰赖氨酰荧光素是天然胆汁酸胆酰甘氨酸的一种荧光类似物。体内和体外研究表明，这种类似物具有许多与胆酰甘氨酸相似的生物学特性。在本研究中，我们分析了6名健康志愿者的胆酰赖氨酰荧光素血浆清除率，将其作为一种潜在的定量肝功能测试。
将注射用水中的该化合物以0.02mg/kg体重的剂量静脉推注给药。
血浆消除曲线显示出快速、中间和缓慢的清除阶段。消除的第一阶段（t1/2 1期）、第二阶段（t1/2 2期）和第三阶段（t1/2 3期）的半衰期分别为1.7±0.9分钟、6.7±1.6分钟和68±17分钟。90分钟时的血浆保留率（%剂量/升血浆）为2.2%。胆酰赖氨酰荧光素的分布容积和60分钟后的残留荧光与其他人对天然或放射性标记胆汁酸获得的数据相似。在6名健康志愿者中的5名中，注射了25倍高剂量的胆酰赖氨酰荧光素（0.5mg/kg体重）以评估该化合物的安全范围。该剂量的消除速率与0.02mg/kg体重剂量的消除速率相似，且未引起任何不良反应。注射前后测量的血清肝功能指标没有显著变化。
本研究表明，胆酰赖氨酰荧光素的清除率与内源性天然胆汁酸的清除率相似，可能潜在地提供一种新的、动态的肝功能测试方法。
