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对急性髓系白血病患者在转换为泊沙康唑片剂制剂前后预防侵袭性真菌感染时达到目标药物水平情况的回顾性分析。

Retrospective analysis of goal drug level attainment of posaconazole for invasive fungal infection prophylaxis in patients with acute myeloid leukemia pre- and post-switch to tablet formulation.

作者信息

Liebenstein Tyler K, Widmer Kristin M, Fallon Michael J

机构信息

Department of Pharmacy, University of Wisconsin Health, Madison, WI, USA.

出版信息

J Oncol Pharm Pract. 2018 Dec;24(8):599-603. doi: 10.1177/1078155217722405. Epub 2017 Aug 2.

Abstract

BACKGROUND

Posaconazole is approved for invasive fungal infection prophylaxis in patients with hematologic malignancies. Posaconazole suspension is plagued by poor oral absorption and dietary requirements that are difficult for patients to meet. The delayed-release tablet formulation of posaconazole may be taken without regards to meals and has significantly better oral absorption than posaconazole suspension.

OBJECTIVES

We sought to determine if a switch to posaconazole tablets improved steady-state drug level attainment for invasive fungal infection prophylaxis in patients with acute myeloid leukemia.

METHODS

All adult inpatients with acute myeloid leukemia undergoing chemotherapy, who received posaconazole for invasive fungal infection prophylaxis between 2012 and 2015, were included. The primary outcome was proportion of patients with first posaconazole level greater than 700 ng/mL. Secondary outcomes included proportion of patients with first posaconazole level greater than 1000 ng/mL, invasive fungal infection within 100 days, and adverse drug events.

RESULTS

Forty patients received posaconazole tablets and 34 patients received suspension. Posaconazole levels were significantly higher at first measurement in patients receiving tablet than suspension (1296 ng/mL vs. 788 ng/mL, p < 0.01). Thirty-seven patients receiving tablets had a serum drug level greater than 700 ng/mL on first measurement versus 18 receiving suspension (p < 0.01). Patients receiving tablets were also more likely to have a serum drug level over 1000 ng/mL on first measurement (26 vs. 11, p < 0.01). Rates of invasive fungal infection and adverse events were not statistically different.

CONCLUSIONS

Patients receiving posaconazole tablets attained significantly higher serum drug levels than those receiving suspension.

摘要

背景

泊沙康唑已被批准用于预防血液系统恶性肿瘤患者的侵袭性真菌感染。泊沙康唑混悬液存在口服吸收差以及患者难以满足的饮食要求等问题。泊沙康唑缓释片制剂服用时无需考虑用餐情况,且口服吸收显著优于泊沙康唑混悬液。

目的

我们试图确定改用泊沙康唑片是否能提高急性髓系白血病患者预防侵袭性真菌感染时达到稳态血药浓度的水平。

方法

纳入2012年至2015年间所有接受化疗且因预防侵袭性真菌感染而接受泊沙康唑治疗的成年急性髓系白血病住院患者。主要结局是首次泊沙康唑血药浓度大于700 ng/mL的患者比例。次要结局包括首次泊沙康唑血药浓度大于1000 ng/mL的患者比例、100天内侵袭性真菌感染情况以及药物不良事件。

结果

40例患者接受泊沙康唑片治疗,34例患者接受混悬液治疗。接受片剂治疗的患者首次测量时的泊沙康唑血药浓度显著高于接受混悬液治疗的患者(1296 ng/mL对788 ng/mL,p<0.01)。37例接受片剂治疗的患者首次测量时血清药物浓度大于700 ng/mL,而接受混悬液治疗的为18例(p<0.01)。接受片剂治疗的患者首次测量时血清药物浓度超过1000 ng/mL的可能性也更高(26例对11例,p<0.01)。侵袭性真菌感染率和不良事件发生率无统计学差异。

结论

接受泊沙康唑片治疗的患者血清药物浓度显著高于接受混悬液治疗的患者。

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