HepQuant tests quantify liver function from clearance of deuterium‐ and 13C‐labeled cholates administered either intravenously and orally (SHUNT) or orally (DuO). Hepatic impairment studies have relied on clinical or laboratory criteria like Child‐Pugh classification to categorize the degree of hepatic dysfunction. We compared HepQuant tests with Child‐Pugh classification in predicting the pharmacokinetics of ampreloxetine. Twenty‐one subjects with hepatic impairment (8 Child‐Pugh A, 7 Child‐Pugh B, and 6 Child‐Pugh C), and 10 age‐ and sex‐matched controls were studied. The pharmacokinetics of ampreloxetine were measured after oral administration of a single dose of 10 mg. Disease severity index (DSI), portal‐systemic shunting (SHUNT%), hepatic reserve, and hepatic filtration rates (HFRs) were measured from serum samples obtained after intravenous administration of [24‐13C]‐cholate and oral administration of [2,2,4,4‐2H]cholate. Ampreloxetine plasma exposure (AUC0‐inf) was similar to controls in Child‐Pugh A, increased 1.7‐fold in subjects with Child‐Pugh B, and 2.5‐fold in subjects with Child‐Pugh C and correlated with both Child‐Pugh score and HepQuant parameters. The variability observed in ampreloxetine exposure (AUC0‐inf) in subjects with moderate (Child‐Pugh B) and severe hepatic impairment (Child‐Pugh C) was explained by HepQuant parameters. Multivariable regression models demonstrated that DSI, SHUNT%, and Hepatic Reserve from SHUNT and DuO were superior predictors of ampreloxetine exposure (AUC0‐inf) compared to Child‐Pugh score. HepQuant DSI, SHUNT%, and hepatic reserve were more useful predictors of drug exposure than Child‐Pugh class for ampreloxetine and thus may better optimize dose recommendations in patients with liver disease. The simple‐to‐administer, oral‐only DuO version of the HepQuant test could enhance clinical utility.

中文翻译：

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通过 HepQuant DuO 量化的肝功能障碍在预测氨普罗西汀的药代动力学方面优于 Child-Pugh 分类

HepQuant 测试通过静脉内和口服 (SHUNT) 或口服 (DuO) 给药的氘和 13C 标记胆酸盐的清除率来量化肝功能。肝功能损害研究依赖于Child-Pugh分类等临床或实验室标准来对肝功能障碍程度进行分类。我们将 HepQuant 测试与 Child-Pugh 分类在预测氨氯西汀的药代动力学方面进行了比较。对 21 名肝功能不全受试者（8 名 Child-Pugh A、7 名 Child-Pugh B 和 6 名 Child-Pugh C）以及 10 名年龄和性别匹配的对照组进行了研究。口服单剂量10 mg后测定氨氯西汀的药代动力学。疾病严重指数（DSI）、门体分流（SHUNT%）、肝储备和肝滤过率（HFR）通过静脉注射[24‐13C]-胆酸盐和口服[2,2,4,4-2H]胆酸盐。氨氯西汀血浆暴露量（AUC0-inf）与 Child-Pugh A 中的对照相似，Child-Pugh B 受试者中增加 1.7 倍，Child-Pugh C 受试者中增加 2.5 倍，并且与 Child-Pugh 评分和 HepQuant 参数相关。氨氯西汀暴露量观察到的变异性（AUC0-inf）在中度（Child-Pugh B）和重度肝损伤（Child-Pugh C）受试者中的结果由 HepQuant 参数解释。多变量回归模型表明，DSI、SHUNT% 以及 SHUNT 和 DuO 的肝储备是氨氯西汀暴露量 (AUC) 的优异预测因子0-inf）与 Child-Pugh 评分相比。 HepQuant DSI、SHUNT% 和肝脏储备是比安普洛西汀 Child‐Pugh 分级更有用的药物暴露预测因子，因此可以更好地优化肝病患者的剂量建议。操作简单、仅口服的 DuO 版本的 HepQuant 测试可以增强临床实用性。