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艾沙康唑的药代动力学新特性。特殊情况下的应用。

Pharmacokinetic novelties of isavuconazole. Use in special situations.

作者信息

Candel Francisco Javier, Matesanz Mayra, Mensa José, Azanza José Ramón

机构信息

Clinical Microbiology and Infectious Diseases, IdISSC & IML Health Research Institutes, Hospital Clínico San Carlos, Madrid, Spain.

Hospital at Home Unit, Department of Internal Medicine, Hospital Clínico San Carlos, Madrid, Spain.

出版信息

Rev Iberoam Micol. 2025 Jan-Mar;42(1):37-44. doi: 10.1016/j.riam.2025.02.003. Epub 2025 Mar 22.

Abstract

Isavuconazole, a next generation triazole, exhibits unique pharmacokinetic and pharmacodynamic properties that make it ideal for treating invasive fungal infections in critically ill and immunocompromised patients. This antifungal agent stands out for its broad spectrum of activity, which includes filamentous fungi such as Aspergillus and Mucorales, with an efficacy comparable to that of voriconazole and additional advantages against these pathogens. Its high oral bioavailability (close to 100%), prolonged half-life (>100h), and linear, predictable pharmacokinetic profile minimize the need for frequent dose adjustments and therapeutic monitoring. Its lipophilic structure facilitates penetration into key tissues, such as the central nervous system and pulmonary tissue, as validated by clinical studies showing survival rates exceeding 70% in patients with complicated invasive fungal infection. Its use is safe in populations with renal impairment, mild to moderate hepatic impairment, paediatrics, and obesity, although dose adjustment is recommended for severe hepatic impairment. Recent studies in critically ill patients undergoing extracorporeal membrane oxygenation or continuous renal replacement therapy have revealed moderate reductions in plasma concentration, without significant clinical impact. Adaptive dosing strategies have been proposed to optimize efficacy in these cases. Compared to other triazoles, isavuconazole demonstrates a robust safety profile, with lower incidences of hepatotoxicity and neurotoxicity. Its antifungal activity, favorable pharmacokinetics, and excellent safety profile underscore its role as a reference antifungal agent, particularly in challenging clinical scenarios.

摘要

艾沙康唑作为新一代三唑类药物,具有独特的药代动力学和药效学特性,使其成为治疗重症和免疫功能低下患者侵袭性真菌感染的理想药物。这种抗真菌药物因其广泛的活性谱而脱颖而出,其活性谱包括丝状真菌,如曲霉和毛霉目真菌,其疗效与伏立康唑相当,并且对这些病原体还有其他优势。它具有高口服生物利用度(接近100%)、较长的半衰期(>100小时)以及线性、可预测的药代动力学特征,从而将频繁调整剂量和治疗监测的需求降至最低。其亲脂性结构有助于渗透到关键组织,如中枢神经系统和肺组织,临床研究证实,患有复杂侵袭性真菌感染的患者生存率超过70%。在肾功能损害、轻度至中度肝功能损害、儿科和肥胖人群中使用是安全的,不过对于严重肝功能损害患者建议调整剂量。最近对接受体外膜肺氧合或持续肾脏替代治疗的重症患者的研究表明,血浆浓度会适度降低,但无明显临床影响。已提出适应性给药策略以在这些情况下优化疗效。与其他三唑类药物相比,艾沙康唑显示出良好的安全性,肝毒性和神经毒性的发生率较低。其抗真菌活性、良好的药代动力学和出色的安全性突出了其作为参考抗真菌药物的作用,特别是在具有挑战性的临床场景中。

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