Department of Medical and Surgical Sciences, Alma Mater Studiorum, University of Bologna, Bologna, Italy.
Clinical Pharmacology Unit, Department for Integrated Infectious Risk Management, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy; and.
Ther Drug Monit. 2023 Apr 1;45(2):140-142. doi: 10.1097/FTD.0000000000001064. Epub 2023 Jan 2.
The authors present a case of a 67-year-old woman with primary biliary cirrhosis (Child-Pugh class B) who was treated with isavuconazole for invasive pulmonary and cerebral aspergillosis. Isavuconazole treatment was initiated with the standard maintenance dose of 200 mg daily. Therapeutic drug monitoring (TDM) was performed to target trough concentrations within the desired range of 1.0-5.13 mg/L.
Real-time TDM and pharmacokinetic analyses were used to determine the dose adjustments. Liver transaminases (alanine aminotransferase and gamma-glutamyl transferase) were assessed to monitor hepatotoxicity.
The trough plasma levels gradually increased over time up to 17.8 mg/L. TDM-guided clinical pharmacological advice was helpful to initially reduce the dose, then to temporarily suspend drug administration, and finally to calculate the correct dose that allowed for long-term treatment up to day 258. No major signs and/or symptoms of drug-related toxicity occurred, apart from a transient increase in gamma-glutamyl transferases that normalized after the drop in isavuconazole trough levels within the desired range.
TDM-guided clinical pharmacological advice was essential for the successful and safe management of isavuconazole treatment in this patient with moderate liver dysfunction.
作者报告了一例 67 岁原发性胆汁性肝硬化（Child-Pugh 分级 B）女性患者，因侵袭性肺和脑曲霉病接受伊曲康唑治疗。伊曲康唑治疗起始剂量为每日 200mg 标准维持剂量。进行治疗药物监测（TDM）以将谷浓度靶向到目标范围内 1.0-5.13mg/L。
采用实时 TDM 和药代动力学分析来确定剂量调整。评估肝转氨酶（丙氨酸氨基转移酶和γ-谷氨酰转移酶）以监测肝毒性。
谷血浆水平随时间逐渐升高，最高达 17.8mg/L。TDM 指导的临床药理学建议有助于最初减少剂量，然后暂时停止药物治疗，最后计算出正确的剂量，从而允许长期治疗至第 258 天。除了伊曲康唑谷浓度在目标范围内下降后γ-谷氨酰转移酶短暂升高外，未发生与药物相关毒性的主要体征和/或症状。
对于中度肝功能障碍患者，TDM 指导的临床药理学建议对于伊曲康唑治疗的成功和安全管理至关重要。
