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质子泵抑制剂和/或类固醇的联合使用可能是血液恶性肿瘤成年患者中泊沙康唑延迟释放片谷浓度较低的一个危险因素。

Co-administration of proton pump inhibitors and/or of steroids may be a risk factor for low trough concentrations of posaconazole delayed-released tablets in adult patients with haematological malignancies.

机构信息

Institute of Clinical Pharmacology, Santa Maria della Misericordia University Hospital, Azienda Sanitaria Universitaria Integrata di Udine, Udine, Italy.

Department of Medicine, University of Udine, Udine, Italy.

出版信息

Br J Clin Pharmacol. 2018 Nov;84(11):2544-2550. doi: 10.1111/bcp.13707. Epub 2018 Aug 19.

Abstract

AIMS

The aim of this study was to determine clinical variables associated with posaconazole exposure among adult patients with haematological malignancies who received posaconazole tablets for prophylaxis of invasive fungal infections (IFIs).

METHODS

The study population included adult patients with haematological malignancies who received posaconazole delayed-release tablets for prophylaxis of IFIs after induction chemotherapy for acute leukaemia or graft-versus-host-disease (GVHD) complicating hematopoietic stem cell transplantation (HSCT) in the period January 2016-December 2017.

RESULTS

Sixty-six consecutive patients with 176 posaconazole C were included for evaluation in the study. Subtherapeutic posaconazole concentrations (< 0.7 mg l ) were observed at least once in 33.3% of patients (22/66), and overall in 17.0% of therapeutic drug monitoring (TDM) episodes (30/176). At multilevel linear regression, use of PPIs (P = 0.008), use of intermediate or high dose steroids (>0.7 mg kg daily) (P = 0.022) and male gender (P = 0.025) were significantly associated with decreased C , whereas time from starting therapy (P = 0.032) was associated with increased C in our patient population.

CONCLUSION

Posaconazole exposure during treatment with delayed-released tablet formulation may be affected by the use of PPIs and/or of intermediate or high dose steroids.

摘要

目的

本研究旨在确定接受泊沙康唑片预防侵袭性真菌感染(IFI)的血液恶性肿瘤成年患者中与泊沙康唑暴露相关的临床变量。

方法

研究人群包括在接受诱导化疗治疗急性白血病或造血干细胞移植(HSCT)后并发移植物抗宿主病(GVHD)的血液恶性肿瘤成年患者中,接受泊沙康唑延迟释放片预防 IFI 的患者。

结果

在研究中,共有 66 例连续患者接受了 176 次泊沙康唑 C 评估。33.3%(22/66)的患者至少有一次观察到治疗性药物监测(TDM)的亚治疗性泊沙康唑浓度(<0.7mg/l),而总浓度为 17.0%(30/176)。在多水平线性回归中,使用质子泵抑制剂(P=0.008)、使用中或高剂量类固醇(>0.7mg/kg/d)(P=0.022)和男性性别(P=0.025)与 C 降低显著相关,而从开始治疗的时间(P=0.032)与我们患者人群中的 C 增加相关。

结论

在使用延迟释放片剂制剂治疗期间,泊沙康唑的暴露可能受到质子泵抑制剂和/或中或高剂量类固醇的影响。

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