Nashimoto Shunsuke, Imai Shungo, Sugawara Mitsuru, Takekuma Yoh
Faculty of Pharmaceutical Sciences, Hokkaido University.
Keio University Faculty of Pharmacy, 1-5-30 Shibakoen.
Biol Pharm Bull. 2023;46(2):230-236. doi: 10.1248/bpb.b22-00608.
The Child-Pugh score is widely used to assess liver function and estimate drug clearance in patients with liver cirrhosis. Recently, the albumin-bilirubin (ALBI) score, which objectively assesses liver function based only on albumin and total bilirubin levels, was developed as a new method. The purpose of this study was to analyze the relationship between the liver function assessment method and the plasma concentration of voriconazole (VRCZ), an antifungal drug for patients with liver cirrhosis. This single-center retrospective study enrolled 159 patients who received VRCZ between 2012 and 2020. In patients administered VRCZ orally, the median concentration to dose (C : D) ratio increased with the progression of Child-Pugh and ALBI grades. Positive correlations between the ALBI score and VRCZ C : D ratio were observed in patients with cirrhosis (r = 0.52 (95% confidence interval, 0.069-0.79); p < 0.05). In addition, a highly negative correlation was observed between the ALBI score and VRCZ daily maintenance dose (r=-0.79 (95% confidence interval, -0.92 to -0.50); p < 0.0001). In contrast, for patients administered VRCZ intravenously, no increase in C : D ratio was observed for both Child-Pugh and ALBI scores compared to the non-liver cirrhosis group. This may be because the injection is often used in severely ill patients, and factors other than impaired liver function may affect the plasma concentrations of VRCZ. In conclusion, the ALBI score was shown to be useful in predicting VRCZ clearance as well as the Child-Pugh score, and the initial dose of VRCZ might be determined according to the ALBI score.
Child-Pugh评分广泛用于评估肝硬化患者的肝功能并估计药物清除率。最近，仅基于白蛋白和总胆红素水平客观评估肝功能的白蛋白-胆红素（ALBI）评分作为一种新方法被开发出来。本研究的目的是分析肝功能评估方法与肝硬化患者抗真菌药物伏立康唑（VRCZ）血浆浓度之间的关系。这项单中心回顾性研究纳入了2012年至2020年间接受VRCZ治疗的159例患者。口服VRCZ的患者中，Child-Pugh和ALBI分级进展时，中位浓度与剂量（C : D）比升高。在肝硬化患者中观察到ALBI评分与VRCZ C : D比呈正相关（r = 0.52（95%置信区间，0.069 - 0.79）；p < 0.05）。此外，观察到ALBI评分与VRCZ每日维持剂量呈高度负相关（r = -0.79（95%置信区间，-0.92至-0.50）；p < 0.0001）。相比之下，对于静脉注射VRCZ的患者，与非肝硬化组相比，Child-Pugh和ALBI评分的C : D比均未升高。这可能是因为注射剂常用于重症患者，肝功能受损以外的因素可能会影响VRCZ的血浆浓度。总之，ALBI评分在预测VRCZ清除率方面与Child-Pugh评分一样有用，VRCZ的初始剂量可能根据ALBI评分来确定。
