Background Posaconazole maintains broad antifungal activity and is employed for prevention and treatment of invasive fungal infections in oncology patients. Older formulations required therapeutic drug monitoring, and specific plasma drug levels have been recommended. This study evaluated factors associated with sub-therapeutic concentrations with the newer delayed-release tablet formulation. Methods In this retrospective, single center cohort study at a national comprehensive cancer center all oncology patients receiving delayed-release posaconazole at standard dosing of 300mg orally per day from 06/2021–07/2023 with plasma drug concentration evaluation were identified. Demographic, clinical and laboratory data were evaluated to identify risk factors associated with sub-therapeutic drug legs at targets of ≥1.25 µg/mL and ≥1.8 µg/mL. Results Of 110 patients identified, 98 met criteria for inclusion into the study. Median time from initiation of posaconazole to drug level assessment was 13 days and median concentration was 1.29 µg/mL. Of the 22 patients receiving posaconazole for prophylaxis 5 (22.7%) failed to achieve concentrations ≥ 0.7 µg/mL and of 76 patients receiving posaconazole for treatment 38 (50%) failed to achieve concentrations of ≥1.25 µg/mL. In multi-variable analysis albumin of ≤3 g/dL and ideal body weight ≥60 kg were found to be associated with sub-therapeutic levels. For a higher target of ≥1.8 µg/mL only albumin ≤3 g/dL was associated with sub-therapeutic levels for variables evaluated. Conclusions A higher initial dosing strategy and therapeutic drug monitoring for oncology patients with albumin ≤3 g/dL receiving posaconazole particularly for the treatment of invasive fungal infection could be considered.

中文翻译：

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肿瘤患者泊沙康唑治疗药物监测的真实世界经验：低白蛋白血症作为亚治疗泊沙康唑水平预测因子的临床意义

背景 泊沙康唑保持广泛的抗真菌活性，用于预防和治疗肿瘤患者的侵袭性真菌感染。较旧的配方需要治疗药物监测，并且已推荐特定的血浆药物水平。这项研究评估了与新型缓释片剂配方的亚治疗浓度相关的因素。方法 在这项回顾性、单中心队列研究中，在一个国家综合癌症中心，确定了 2021 年 6 月至 2023 年 7 月期间接受标准剂量每天口服 300 毫克缓释泊沙康唑并进行血浆药物浓度评估的所有肿瘤患者。对人口统计学、临床和实验室数据进行评估，以确定与目标≥1.25 µg/mL 和≥1.8 µg/mL 的亚治疗药物腿相关的风险因素。结果 在确定的 110 名患者中，98 名符合纳入研究的标准。从泊沙康唑开始使用到药物水平评估的中位时间为 13 天，中位浓度为 1.29 µg/mL。在接受泊沙康唑预防的 22 名患者中，有 5 名 (22.7%) 未能达到浓度≥ 0.7 µg/mL，在接受泊沙康唑治疗的 76 名患者中，有 38 名 (50%) 未能达到浓度 ≥ 1.25 µg/mL。在多变量分析中，发现白蛋白≤3 g/dL 和理想体重≥60 kg 与亚治疗水平相关。对于≥1.8 µg/mL 的较高目标，仅白蛋白≤3 g/dL 与所评估变量的亚治疗水平相关。结论 对于接受泊沙康唑治疗的白蛋白≤3 g/dL 的肿瘤患者，特别是用于治疗侵袭性真菌感染的患者，可以考虑采用更高的初始剂量策略和治疗药物监测。