Handley Guy, Greene John, Cannella Anthony P, Velez Ana Paula, Shah Shivan, Pasikhova Yanina
Division of Infectious Disease and International Medicine, Department of Internal Medicine, Morsani College of Medicine, University of South Florida, Tampa, Florida, USA.
H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida, USA.
Open Forum Infect Dis. 2024 Mar 29;11(5):ofae185. doi: 10.1093/ofid/ofae185. eCollection 2024 May.
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 subtherapeutic concentrations with the newer delayed-release tablet formulation.
In this retrospective, single-center cohort study at a national comprehensive cancer center, all oncology patients receiving delayed-release posaconazole at standard dosing of 300 mg orally per day from 06/2021 to 07/2023 with plasma drug concentration evaluation were identified. Demographic, clinical, and laboratory data were evaluated to identify risk factors associated with subtherapeutic drug levels at targets of ≥1.25 µg/mL and ≥1.8 µg/mL.
Of 110 patients identified, 98 met criteria for inclusion in the study. The median time from initiation of posaconazole to drug level assessment was 13 days, and the 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 multivariable analysis, albumin of ≤3 g/dL and ideal body weight ≥60 kg were found to be associated with subtherapeutic levels. For a higher target of ≥1.8 µg/mL, only albumin ≤3 g/dL was associated with subtherapeutic levels for the variables evaluated.
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.
泊沙康唑具有广泛的抗真菌活性，用于预防和治疗肿瘤患者的侵袭性真菌感染。旧剂型需要进行治疗药物监测，并推荐了特定的血浆药物水平。本研究评估了新型缓释片剂剂型下与治疗浓度不足相关的因素。
在一家全国性综合癌症中心进行的这项回顾性单中心队列研究中，确定了2021年6月至2023年7月期间所有接受标准剂量每日口服300mg缓释泊沙康唑并进行血浆药物浓度评估的肿瘤患者。评估人口统计学、临床和实验室数据，以确定与目标治疗浓度不足相关的危险因素，目标浓度分别为≥1.25μg/mL和≥1.8μg/mL。
在确定的110例患者中，98例符合纳入研究的标准。从开始使用泊沙康唑到进行药物水平评估的中位时间为13天，中位浓度为1.29μg/mL。在22例接受泊沙康唑预防的患者中，5例（22.7%）未达到浓度≥0.7μg/mL；在76例接受泊沙康唑治疗的患者中，38例（50%）未达到浓度≥1.25μg/mL。多变量分析发现，白蛋白≤3g/dL和理想体重≥60kg与治疗浓度不足有关。对于更高的目标浓度≥1.8μg/mL，在所评估的变量中，只有白蛋白≤3g/dL与治疗浓度不足有关。
对于接受泊沙康唑治疗的白蛋白≤3g/dL的肿瘤患者，尤其是侵袭性真菌感染的治疗患者，可考虑采用更高的初始给药策略并进行治疗药物监测。
