Retrospective Comparison of Posaconazole Levels in Patients Taking the Delayed-Release Tablet versus the Oral Suspension
Retrospective Comparison of Posaconazole Levels in Patients Taking the Delayed-Release Tablet versus the Oral Suspension
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DOI：
10.1128/aac.00496-15
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发表时间：
2015-08-01
影响因子：
4.9
通讯作者：
Tande, Aaron J.
中科院分区：
文献类型：
--
作者：
Durani, Urshila;Tosh, Pritish K.;Tande, Aaron J.
与氟康唑相比，泊沙康唑预防性治疗可降低侵袭性真菌感染的风险，但口服混悬剂的低生物利用度限制了其疗效。一种新的延迟释放片剂在健康志愿者中表现出改善的药代动力学特征。然而，尚未在临床实践中比较两种制剂的血清水平。本研究比较了泊沙康唑缓释片和口服混悬剂的疗效。这项回顾性队列研究纳入了2012年至2014年期间开始接受泊沙康唑治疗的93例患者，并测量了至少一种血清泊沙康唑水平。主要指标是达到初始治疗水平（>700 ng/ml）的患者比例。泊沙康唑的初始治疗水平在29/32例（91%）接受片剂的患者和37/61例（61%）接受混悬液的患者中观察到（P = 0.003）。在开始治疗后5至14天测量稳态水平的患者中，在20例接受片剂治疗的患者中有18例（90%）和43例接受混悬液治疗的患者中有25例（58%）观察到治疗水平（P = 0.01）。在这些患者中，片剂队列的泊沙康唑中位水平（1655 ng/ml）是混悬剂队列（798 ng/ml）的两倍（P = 0.004）。在这项队列研究中，泊沙康唑缓释片的生物利用度提高，导致达到治疗血清水平的患者比例显著高于接受口服混悬剂的队列。本研究的结果强烈支持在有侵袭性真菌感染风险的患者中使用延迟释放片剂而不是混悬剂。
While posaconazole prophylaxis decreases the risk of invasive fungal infection compared to fluconazole, low bioavailability of the oral-suspension formulation limits its efficacy. A new delayed-release tablet formulation demonstrated an improved pharmacokinetic profile in healthy volunteers. However, serum levels for the two formulations have not been compared in clinical practice. This study compared achievement of therapeutic posaconazole levels in patients taking the delayed-release tablet to those taking the oral suspension. This retrospective cohort study included 93 patients initiated on posaconazole between 2012 and 2014 and had at least one serum posaconazole level measured. The primary measure was the proportion of patients achieving an initial therapeutic level (>700 ng/ml). An initial therapeutic posaconazole level was seen in 29 of 32 (91%) patients receiving tablets and 37 of 61 (61%) patients receiving suspension (P = 0.003). Among patients with a steady-state level measured 5 to 14 days after initiation, a therapeutic level was observed in 18 of 20 (90%) patients receiving tablets and 25 of 43 (58%) patients receiving suspension (P = 0.01). In these patients, the median posaconazole level of the tablet cohort (1655 ng/ml) was twice that of the suspension cohort (798 ng/ml) (P = 0.004). In this cohort study, the improved bioavailability of delayed-release posaconazole tablets translates into a significantly higher proportion of patients achieving therapeutic serum levels than in the cohort receiving the oral suspension. The results of this study strongly support the use of delayed-release tablets over suspension in patients at risk for invasive fungal infection.