Background & Aims

Solute generation rates, distribution volumes and compartment effects control the in vivo efficiency of any extracorporeal therapy such as extracorporeal liver support (ELS) used to remove bile acids accumulating in acute-on-chronic liver patients. The aim of this study was to identify and to examine kinetic parameters of two major bile acids using mathematical modeling.

Methods

The kinetics of cholic (CA) and chenodeoxycholic acid (CDCA) were described by one- and two-compartment models with central elimination by decreasing or constant extracorporeal clearance, constant bile acid generation rate, and constant apparent distribution volume. Concentration profiles collected in 13 ELS sessions done in 8 patients were included for model calculations

Results

For the one-compartment model, the average volumes and generation rates were 30 ± 6 [l], 0.19 ± 0.06 [μmol/min] for CA and 22 ± 5 [l], 0.29 ± 0.08 [μmol/min] for CDCA, respectively. For the one-compartment model and average normalized concentrations, the volumes and generation rates were 25 [l], 0.28 [μmol/min] for CA and 18 [l], 0.37 [μmol/min] for CDCA, respectively. For the two-compartment model, average normalized concentrations, the same initial concentration in both compartments, and assuming a 10% post-treatment rebound, the volume and generation rates were 25 [l], 0.27 [μmol/min] for CA and 19 [l], 0.32 [μmol/min] for CDCA, respectively.

Conclusions

The generation rate for CDCA is higher when compared to that of CA and independent of the number of compartments. Assuming a constant extracorporeal clearance overestimates generation rate and distribution volume. The kinetic parameters of one- and two-compartment models are comparable for the same bile acid.

中文翻译：

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终末期肝支持患者的胆汁酸动力学模型

背景与目标

溶质的产生速率，分布体积和隔室效应控制着任何体外疗法的体内效率，例如体外肝脏支持（ELS）用于去除急性慢性肝病患者体内积聚的胆汁酸。这项研究的目的是使用数学模型识别和检查两种主要胆汁酸的动力学参数。

方法

胆汁（CA）和鹅去氧胆酸（CDCA）的动力学由一室和两室模型描述，通过减少或保持恒定的体外清除率，保持恒定的胆汁酸产生速率和保持恒定的表观分布体积来进行中心消除。模型计算中包括了在8例患者中进行的13次ELS会话中收集的浓度曲线

结果

对于一室模型，平均体积和生成速率分别为30±6 [l]，CA 0.19±0.06 [μmol/ min]和22±5 [l]，CDCA 0.29±0.08 [μmol/ min]，分别。对于一室模型和平均归一化浓度，CA的体积和生成速率分别为25 [l]，0.28 [μmol/ min]和CDCA的分别为18 [l]，0.37 [μmol/ min]。对于两室模型，平均归一化浓度，两个室中的初始浓度相同，并且假设处理后回弹为10％，则CA的体积和生成速率分别为25 [l]，0.27 [μmol/ min]和19 [1]，对于CDCA分别为0.32 [μmol/ min]。

结论

与CA相比，CDCA的生成率更高，并且与间隔数无关。假设恒定的体外清除率会高估发生率和分布量。对于相同的胆汁酸，一室和两室模型的动力学参数是可比的。