Sydney Pharmacy School, Faculty of Medicine and Health, The University of Sydney, Camperdown, NSW, Australia.
Westmead Hospital, Westmead, NSW, Australia.
Ther Drug Monit. 2022 Feb 1;44(1):198-214. doi: 10.1097/FTD.0000000000000931.
Reduced exposure to echinocandins has been reported in specific patient populations, such as critically ill patients; however, fixed dosing strategies are still used. The present review examines the accumulated evidence supporting echinocandin therapeutic drug monitoring (TDM) and summarizes available assays and sampling strategies.
A literature search was conducted using PubMed in December 2020, with search terms such as echinocandins, anidulafungin, caspofungin, micafungin, or rezafungin with pharmacology, pharmacokinetics (PKs), pharmacodynamics (PDs), drug-drug interactions, TDM, resistance, drug susceptibility testing, toxicity, adverse drug reactions, bioanalysis, chromatography, and mass spectrometry. Data on PD/PD (PK/PD) outcome markers, drug resistance, PK variability, drug-drug interactions, assays, and TDM sampling strategies were summarized.
Echinocandins demonstrate drug exposure-efficacy relationships, and maximum concentration/minimal inhibitory concentration ratio (Cmax/MIC) and area under the concentration-time curve/MIC ratio (AUC/MIC) are proposed PK/PD markers for clinical response. The relationship between drug exposure and toxicity remains poorly clarified. TDM could be valuable in patients at risk of low drug exposure, such as those with critical illness and/or obesity. TDM of echinocandins may also be useful in patients with moderate liver impairment, drug-drug interactions, hypoalbuminemia, and those undergoing extracorporeal membrane oxygenation, as these conditions are associated with altered exposure to caspofungin and/or micafungin. Assays are available to measure anidulafungin, micafungin, and caspofungin concentrations. A limited-sampling strategy for anidulafungin has been reported.
Echinocandin TDM should be considered in patients at known risk of suboptimal drug exposure. However, for implementing TDM, clinical validation of PK/PD targets is needed.
据报道，在某些特定患者群体中，如危重症患者，会减少使用棘白菌素类药物，但仍在使用固定剂量策略。本综述考察了支持棘白菌素类药物治疗药物监测（TDM）的累积证据，并总结了现有的检测方法和采样策略。
于 2020 年 12 月在 PubMed 上进行文献检索，使用的检索词包括棘白菌素类药物、阿尼芬净、卡泊芬净、米卡芬净或瑞他康唑，与药理学、药代动力学（PK）、药效动力学（PD）、药物-药物相互作用、TDM、耐药性、药物敏感性测试、毒性、不良反应、生物分析、色谱和质谱相关。总结了 PD/PD（PK/PD）结局标志物、耐药性、PK 变异性、药物-药物相互作用、检测方法和 TDM 采样策略的数据。
棘白菌素类药物显示出药物暴露与疗效的关系，最大浓度/最小抑菌浓度比值（Cmax/MIC）和浓度时间曲线下面积/最小抑菌浓度比值（AUC/MIC）被提议作为临床反应的 PK/PD 标志物。药物暴露与毒性之间的关系仍不清楚。在药物暴露风险低的患者中，如患有危重病和/或肥胖症的患者，TDM 可能具有重要价值。在药物暴露中度受损、药物-药物相互作用、低白蛋白血症和接受体外膜氧合的患者中，TDM 也可能有用，因为这些情况与卡泊芬净和/或米卡芬净的暴露改变有关。现已有用于检测阿尼芬净、米卡芬净和卡泊芬净浓度的检测方法。据报道，阿尼芬净的有限采样策略已被报道。
应考虑在已知药物暴露不足风险的患者中进行棘白菌素类药物 TDM。然而，在实施 TDM 时，需要对 PK/PD 靶标进行临床验证。
