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首页> 外文期刊>Antimicrobial agents and chemotherapy. >Effect of mild and moderate liver disease on the pharmacokinetics of isavuconazole after intravenous and oral administration of a single dose of the prodrug BAL8557.
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Effect of mild and moderate liver disease on the pharmacokinetics of isavuconazole after intravenous and oral administration of a single dose of the prodrug BAL8557.

机译：静脉和口服单剂量前药BAL8557后，轻度和中度肝病对伊沙康康唑药代动力学的影响。

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Isavuconazole is a promising new antifungal drug with favorable pharmacokinetic properties and excellent activity against a number of fungi. It is administered as a water-soluble prodrug (BAL8557) that is cleaved by plasma esterases to isavuconazole, which is eliminated primarily by hepatic metabolism. The objective of this investigation was to assess the effect of alcohol-related liver disease on the pharmacokinetics of isavuconazole. Subjects were 16 healthy individuals, 16 with mild liver impairment, and 16 with moderate liver impairment who were randomized to receive a single oral or intravenous dose of BAL8557 equivalent to 100 mg isavuconazole. Blood samples were collected for 21 days following drug administration, and plasma concentrations of isavuconazole, BAL8557, and the cleavage product BAL8728 were measured using high-pressure liquid chromatography coupled with tandem mass spectrometry. Following intravenous administration, the half-life of isavuconazole increased from 123 h for healthy volunteers to 224 h and 302 h for subjects with mild and moderate liver impairment, respectively. The systemic clearance of isavuconazole following intravenous administration decreased from 2.73 liters/h for healthy subjects to 1.43 liters/h for subjects with moderate liver impairment (47.6% decrease [P < 0.05]). A similar decrease (23.5%) was observed after oral administration. These results suggest that a dose adjustment may be needed when isavuconazole is used to treat fungal infections in patients with liver disease.
机译：Isavuconazole是一种有前途的新型抗真菌药物，具有良好的药代动力学特性，并且对多种真菌均具有出色的活性。它以水溶性前药（BAL8557）的形式给药，可被血浆酯酶裂解为艾伐康唑，后者主要通过肝代谢消除。这项研究的目的是评估酒精相关性肝病对伊沙康康唑药代动力学的影响。受试者为16名健康个体，其中16名患有轻度肝功能不全，而16名患有中度肝功能不全，他们随机接受单次口服或静脉内BAL8557剂量，相当于100毫克依沙康康。给药后21天收集血液样品，并使用高压液相色谱-串联质谱法测定伊沙康康唑，BAL8557和裂解产物BAL8728的血浆浓度。静脉内给药后，伊沙康康唑的半衰期从健康志愿者的123小时延长至轻度和中度肝功能不全受试者的224小时和302小时。静脉注射伊沙康康唑后的全身清除率从健康受试者的2.73升/小时降低至中度肝功能不全受试者的1.43升/小时（降低47.6％[P <0.05]）。口服后观察到类似的下降（23.5％）。这些结果表明，当使用艾沙康康唑治疗肝病患者的真菌感染时，可能需要调整剂量。

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