Effect of posaconazole combined with proton pump inhibitors on blood concentrations and invasive fungal infection in patients with malignant hematological disorders

QU Ruochen; YU Jing; WANG Ziyang; LIU Minglin; LIU Jiahui; LIU Xinying; CUI Xinyu; WANG Ziyi; LIU Yan

doi:10.6039/j.issn.1001-0408.2023.10.16

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Effect of posaconazole combined with proton pump inhibitors on blood concentrations and invasive fungal infection in patients with malignant hematological disorders

更新时间：2025-09-27

- Effect of posaconazole combined with proton pump inhibitors on blood concentrations and invasive fungal infection in patients with malignant hematological disorders
- ZHONGGUO YAOFANG Vol. 34, Issue 10, Pages: 1237-1241(2023)
- 作者机构：
  
  1.河北医科大学第一医院临床药学部，石家庄　050000
  2.河北省人工智能临床药学技术创新中心，石家庄　050000
  3.河北医科大学药学院，石家庄　050000
  4.河北医科大学第一医院血液内科，石家庄　050000
- 作者简介：
- 基金信息：
- DOI：10.6039/j.issn.1001-0408.2023.10.16
  CLC： R969.3
- Received：29 August 2022，
  
  Revised：2023-04-24，
  
  Accepted：24 April 2023，
  
  Published：30 May 2023
- 稿件说明：
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屈若尘,于静,王子阳,等.泊沙康唑联用PPI对恶性血液病患者血药浓度和侵袭性真菌感染的影响[J].中国药房,2023,34(10):1237-1241.

QU Ruochen,YU Jing,WANG Ziyang,et al.Effect of posaconazole combined with proton pump inhibitors on blood concentrations and invasive fungal infection in patients with malignant hematological disorders[J].ZHONGGUO YAOFANG,2023,34(10):1237-1241.
屈若尘,于静,王子阳,等.泊沙康唑联用PPI对恶性血液病患者血药浓度和侵袭性真菌感染的影响[J].中国药房,2023,34(10):1237-1241. DOI： 10.6039/j.issn.1001-0408.2023.10.16.

QU Ruochen,YU Jing,WANG Ziyang,et al.Effect of posaconazole combined with proton pump inhibitors on blood concentrations and invasive fungal infection in patients with malignant hematological disorders[J].ZHONGGUO YAOFANG,2023,34(10):1237-1241. DOI： 10.6039/j.issn.1001-0408.2023.10.16.

摘要

目的

探讨泊沙康唑联用质子泵抑制剂（PPI）对恶性血液病患者血药浓度和侵袭性真菌病（IFD）发生风险的影响。

方法

选择2020年12月－2021年12月我院血液内科收治的恶性血液病患者40例，按随机数字表法分为对照组（20例）和观察组（20例）。对照组患者给予泊沙康唑口服混悬液，观察组患者给予泊沙康唑口服混悬液联合PPI。比较两组患者的IFD发生率，血药浓度达标率，发生IFD预防到突破时间，IFD相关病死率，感染患者治疗情况及两组患者服用泊沙康唑第7、14、21、28 天的血药浓度；记录两组患者用药期间的不良事件发生情况。

结果

观察组有2例患者、对照组有9例患者因服用泊沙康唑不足7 d即出院而终止研究。观察组患者的IFD发生率显著高于对照组，血药浓度达标率显著低于对照组（

＜0.05）。两组患者发生IFD预防到突破时间、IFD相关病死率、感染患者治疗情况、不良事件发生率比较，差异均无统计学意义（

＞0.05）。用药第7 天，观察组患者的泊沙康唑血药浓度显著低于对照组（

＜0.05）；用药第14天，两组患者的泊沙康唑血药浓度比较，差异无统计学意义（

＞0.05）。

结论

泊沙康唑联用PPI可降低恶性血液病患者的血药浓度，增加IFD发生风险，临床应尽量避免二者联用或在治疗药物监测指导下联用。

Abstract

OBJECTIVE

To explore the effects of posaconazole combined with proton pump inhibitors （PPI） on the blood concentration and the risk of invasive fungal disease （IFD） in patients with malignant hematological disorder.

METHODS

In accordance with the random number table method， 40 patients with malignant hematological disorders who were admitted to the hematology department of our hospital between December 2020 and December 2021 were chosen and divided into control group （20 cases） and observation group （20 cases）. The control group received Posaconazole oral suspension alone， while the observation group received Posaconazole oral suspension combined with PPI. The incidence of IFD， attainment rate of blood concentration， the time from the start of prophylaxis to IFD onset， the fatality associated with IFD， treatment of infected patients， and blood concentrations of posaconazole on 7th， 14th， 21st， and 28th day after posaconazole application were compared between 2 groups； the occurrence of adverse events during drug administration in the two groups was recorded.

RESULTS

The study was stopped because 2 patients in the observation group and 9 patients in the control group received hospital departures after taking posaconazole for fewer than 7 days. The incidence of IFD in the observation group was significantly higher than control group， and the attainment rate of blood concentration in the observation group was significantly lower than control group （

＜0.05）. There was no significant difference in the time from the start of prophylaxis to IFD onset， the fatality associated with IFD， treatment of infected patients and the incid

ence of adverse events （

＞0.05）. The blood concentration of posaconazole in the observation group was significantly lower than control group on 7th day of medication （

＜0.05）； there was no significant in blood concentration of posaconazole between 2 groups on the 14th day of medication （

＞0.05）.

CONCLUSIONS

Posaconazole combined with PPI can reduce the blood concentration of patients with malignant hematological disorders， increase the risk of IFD. Clinical practice should try to avoid the combination of the two or use them under the guidance of therapeutic drug monitoring.

关键词

Keywords

references

SUN Y ， HUANG H ， CHEN J ， et al . Invasive fungal infection in patients receiving chemotherapy for hematological malignancy：a multicenter，prospective，observational study in China [J ] . Tumour Biol ， 2015 ， 36 （ 2 ）： 757 - 767 .

泊沙康唑临床应用专家组 . 泊沙康唑临床应用专家共识 [J ] . 国际呼吸杂志， 2020 ， 40 （ 4 ）： 241 - 261 .

中国医师协会血液科医师分会，中国侵袭性真菌感染工作组 . 血液病/恶性肿瘤患者侵袭性真菌病的诊断标准与治疗原则：第六次修订版 [J ] . 中华内科杂志， 2020 ， 59 （ 10 ）： 754 - 763 .

PECHLIVANOGLOU P ， LE H H ， DAENEN S ， et al . Mixed treatment comparison of prophylaxis against invasive fungal infections in neutropenic patients receiving therapy for haematological malignancies：a systematic review [J ] . J Antimicrob Chemother ， 2014 ， 69 （ 1 ）： 1 - 11 .

JANG S H ， COLANGELO P M ， GOBBURU J V S . Exposure-response of posaconazole used for prophylaxis against invasive fungal infections：evaluating the need to adjust doses based on drug concentrations in plasma [J ] . Clin Pharmacol Ther ， 2010 ， 88 （ 1 ）： 115 - 119 .

HENS B ， BROUWERS J ， CORSETTI M ， et al . Super-saturation and precipitation of posaconazole upon entry in the upper small intestine in humans [J ] . J Pharm Sci ， 2016 ， 105 （ 9 ）： 2677 - 2684 .

国家卫生健康委员会 . 质子泵抑制剂临床应用指导原则：2020年版 [J ] . 中国实用乡村医生杂志， 2021 ， 28 （ 1 ）： 1 - 9 .

JIA M M ， ZHANG Q W ， QIN Z F ， et al . Deciphering the relationship between the trough concentration of posacona-zole and its efficacy and safety in Chinese patients with hematological disorders [J ] . Front Pharmacol ， 2020 ， 11 ： 575463 .

LI X Q ， ANDERSSON T B ， AHLSTRÖM M ， et al . Comparison of inhibitory effects of the proton pump-inhibiting drugs omeprazole，esomeprazole，lansoprazole，pantoprazole，and rabeprazole on human cytochrome P450 activities [J ] . Drug Metab Dispos ， 2004 ， 32 （ 8 ）： 821 - 827 .

中国药学会医院药学专业委员会，中华医学会临床药学分会 . 质子泵抑制剂优化应用专家共识 [J ] . 中国医院药学杂志， 2020 ， 40 （ 21 ）： 2195 - 2213 .

CHEN L ， KREKELS E H J ， VERWEIJ P E ， et al . Pharmacokinetics and pharmacodynamics of posaconazole [J ] . Drugs ， 2020 ， 80 （ 7 ）： 671 - 695 .

COJUTTI PG ， CANDONI A ， LAZZAROTTO D ， et al . 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 [J ] . Br J Clin Pharmacol ， 2018 ， 84 （ 11 ）： 2544 - 2550 .

WALRAVENS J ， BROUWERS J ， SPRIET I ， et al . Effect of pH and comedication on gastrointestinal absorption of posaconazole：monitoring of intraluminal and plasma drug concentrations [J ] . Clin Pharmacokinet ， 2011 ， 50 （ 11 ）： 725 - 734 .

ALFFENAAR J W ， VAN ASSEN S ， VAN DER WERF T S ， et al . Omeprazole significantly reduces posaconazole serum trough level [J ] . Clin Infect Dis ， 2009 ， 48 （ 6 ）： 839 .

CHAU M M ， KONG D C ， VAN HAL S J ， et al . Consensus guidelines for optimising antifungal drug delivery and monitoring to avoid toxicity and improve outcomes in patients with haematological malignancy，2014 [J ] . Intern Med J ， 2014 ， 44 （ 12 b）： 1364 - 1388 .

ÖZKOCAMAN V ， ÖZKALEMKAŞ F ， SEYHAN S ， et al . The outcome of antifungal prophylaxis with posaconazole in patients with acute myeloid leukemia：a single-center study [J ] . Turk J Haematol ， 2018 ， 35 （ 4 ）： 277 - 282 .

LECLERC E ， COMBAREL D ， UZUNOV M ， et al . Prevention of invasive aspergillus fungal infections with the suspension and delayed-release tablet formulations of posaconazole in patients with haematologic malignancies [J ] . Sci Rep ， 2018 ， 8 （ 1 ）： 1681 .

张飞雨，张瑞霞，宋学武，等 . 影响泊沙康唑血药浓度相关因素的研究进展 [J ] . 中国医院药学杂志， 2021 ， 41 （ 9 ）： 971 - 976 .

泊沙康唑临床应用专家组 . 泊沙康唑临床应用专家共识： 2022版 [J ] . 中华临床感染病杂志， 2022 ， 15 （ 5 ）： 321 - 332 .

中华医学会，中华医学会杂志社，中华医学会消化病学分会，等 . 药物性肝损伤基层诊疗指南：2019年 [J ] . 中华全科医师杂志， 2020 ， 19 （ 10 ）： 868 - 875 .

O'FLYNN R ， ZHOU Y P ， WASKIN H ， et al . Hepatic safety of the antifungal triazole agent posaconazole： characterization of adverse event reports in a manufa-cturer’s safety database [J ] . Expert Opin Drug Saf ， 2022 ， 21 （ 8 ）： 1113 - 1120 .

中国临床肿瘤学会抗淋巴瘤联盟，中国临床肿瘤学会抗白血病联盟，中华医学会血液学分会，等 . 恶性血液病患者药物性肝损伤的预防和规范化治疗中国专家共识：2021年版 [J ] . 中华血液学杂志， 2021 ， 42 （ 3 ）： 185 - 192 .

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