泊沙康唑口服混悬液在HSCT患者中的剂量校正浓度及其影响因素分析

董琳; 束一朔; 董中华; 衣巧艳; 李洪娟; 顾艳; 韩燕; 丁国玉; 赵羽琦; 张潇月; 李雪; 林子云; 穆锴; 杨依磊; 时海燕; 王红美

doi:10.6039/j.issn.1001-0408.2023.24.12

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泊沙康唑口服混悬液在HSCT患者中的剂量校正浓度及其影响因素分析

药物与临床 | 更新时间：2023-12-22

- 泊沙康唑口服混悬液在HSCT患者中的剂量校正浓度及其影响因素分析
- Dose-adjusted concentrations of Posaconazole oral suspension in hematopoietic stem cell transplantation patients and analysis of the influential factors
- 中国药房 2023年34卷第24期页码：3025-3029
- 作者机构：
  
  1.山东第一医科大学第一附属医院（山东省千佛山医院）血液病学科，济南　250014
  2.山东第一医科大学第一附属医院（山东省千佛山医院）临床药学科/山东省儿童药物临床评价与研发工程技术研究中心/山东省医药卫生临床药学重点实验室，济南　250014
  3.山东第一医科大学第一附属医院（山东省千佛山医院）小儿内科/山东省儿童药物临床评价与研发工程技术研究中心，济南　250014
- 作者简介：
  
  副主任医师，硕士。研究方向：血液病诊治。E-mail：13583107822@163.com
  主任医师，博士。研究方向：儿科疾病诊治。E-mail：whtwhm@yeah.net
- 基金信息：
  
  国家重点研发计划项目(2020YFC2008303;2020YFC2008306)
- DOI：10.6039/j.issn.1001-0408.2023.24.12
  中图分类号： R978.5
- 纸质出版日期：2023-12-30，
  
  收稿日期：2023-07-10，
  
  修回日期：2023-11-15，
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董琳,束一朔,董中华等.泊沙康唑口服混悬液在HSCT患者中的剂量校正浓度及其影响因素分析 ^Δ[J].中国药房,2023,34(24):3025-3029.

DONG Lin,SHU Yishuo,DONG Zhonghua,et al.Dose-adjusted concentrations of Posaconazole oral suspension in hematopoietic stem cell transplantation patients and analysis of the influential factors[J].ZHONGGUO YAOFANG,2023,34(24):3025-3029.
董琳,束一朔,董中华等.泊沙康唑口服混悬液在HSCT患者中的剂量校正浓度及其影响因素分析 ^Δ[J].中国药房,2023,34(24):3025-3029. DOI： 10.6039/j.issn.1001-0408.2023.24.12.

DONG Lin,SHU Yishuo,DONG Zhonghua,et al.Dose-adjusted concentrations of Posaconazole oral suspension in hematopoietic stem cell transplantation patients and analysis of the influential factors[J].ZHONGGUO YAOFANG,2023,34(24):3025-3029. DOI： 10.6039/j.issn.1001-0408.2023.24.12.

摘要

目的

分析泊沙康唑口服混悬液在造血干细胞移植（HSCT）患者中的剂量校正浓度，并分析其影响因素。

方法

收集2021年1月至2023年4月山东第一医科大学第一附属医院（山东省千佛山医院）收治的服用泊沙康唑口服混悬液预防侵袭性真菌病（IFD）并行泊沙康唑血药浓度监测的住院HSCT患者的临床资料。评估泊沙康唑预防IFD的浓度达标率和临床失败率，并对该药剂量校正浓度（

）的影响因素进行单因素和多元线性回归分析。

结果

共纳入44例患者，患者的泊沙康唑平均谷浓度（

）为（0.99±0.94）µg/mL，有20例患者的

不低于0.7 μg/mL，泊沙康唑预防IFD的浓度达标率为45.45%；13例为临床失败，临床失败率为29.55%。在

未达标的24例患者中，有7例患者及时调整了泊沙康唑剂量，但仍有1例为临床失败；13例未进行剂量调整的患者中，有7例为临床失败；其余4例患者更换了抗真菌药物。单因素分析结果显示，患者性别、体重指数（BMI）、肾功能和联用苯妥英钠、奥美拉唑、甲氧氯普胺对泊沙康唑

有显著影响（

＜0.05）；多元线性回归分析结果显示，性别、BMI和联用苯妥英钠是影响泊沙康唑

的独立因素（

＜0.05）。

结论

泊沙康唑口服混悬液血药浓度个体差异较大；性别、BMI和联用苯妥英钠是影响泊沙康唑

的独立因素。

Abstract

OBJECTIVE

To analyze the dose-adjusted concentrations of Posaconazole oral suspension in patients undergoing hematopoietic stem cell transplantation （HSCT） and their influential factors.

METHODS

Data were collected from hospitalized HSCT patients admitted to the First Affiliated Hospital of Shandong First Medical University （Shandong Provincial Qianfoshan Hospital） from January 2021 to April 2023 who took Posaconazole oral suspension for the prevention of invasive fungal disease （IFD） and received blood concentration of posaconazole. The rate of concentration attainment and clinical failure rate of posaconazole for the prevention of IFD were evaluated， and one-way and multiple linear regression analyses were performed for the influential factors of dose-adjusted concentrations （

） of posaconazole.

RESULTS

A total of 44 patients were enrolled； the mean

of posaconazole in patients was （0.99±0.94） µg/mL， and 20 patients had a

≥0.7 μg/mL， with a concentration attainment rate of 45.45% for the prevention of IFD； 13 cases were clinical failures， with a clinical failure rate of 29.55%. Of 24 patients who did not achieve

of posaconazole for IFD prophylaxis， one patient was a clinical failure despite timely dose adjustment of posaconazole in seven patients； seven of the thirteen patients who did not undergo dose adjustment were clinical failures； and the remaining four patients were switched to other antifungal agents. The results of univariate analysis showed that gender， body mass index （BMI）， renal function， combined use of sodium phenytoin， omeprazole and metoclopramide had a significant effect on the

of posaconazole （

＜0.05）； the results of multivariate linear regression analysis showed that gender， BMI and combined use of sodium phenytoin were the independent factors affecting the

of posaconazole （

＜0.05）.

CONCLUSIONS

Significant individual differences are reflected in the blood concentration of Posaconazole oral suspension； gender， BMI and combined use of sodium phenytoin are independent factors affecting the

of posaconazole.

关键词

泊沙康唑剂量校正浓度影响因素造血干细胞移植治疗药物监测

Keywords

dose-adjusted concentrationinfluential factorhematopoietic stem cell transplantationtherapeutic drug monitoring

references

MARKS D I，LIU Q F，SLAVIN M. Voriconazole for prophylaxis of invasive fungal infections after allogeneic hematopoietic stem cell transplantation[J]. Expert Rev Anti Infect Ther， 2017， 15（5）：493-502.

彭英楠，边志磊，曹伟杰，等. 泊沙康唑与伏立康唑预防异基因造血干细胞移植后侵袭性真菌感染的疗效和安全性[J]. 实用医学杂志，2023，39（6）：742-746.

PENG Y N，BIAN Z L，CAO W J，et al. Efficacy and safety study of posaconazole and voriconazole for the prevention of invasive fungal infections after allogeneic hematopoietic stem cell transplantation[J]. J Pract Med，2023，39（6）：742-746.

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

EIDEN C，MENIANE J C，PEYRIÈRE H，et al. Therapeutic drug monitoring of posaconazole in hematology adults under posaconazole prophylaxis：influence of food intake[J]. Eur J Clin Microbiol Infect Dis，2012，31（2）：161-167.

金磊，徐文彬，叶晨静，等. 泊沙康唑对血液恶性肿瘤化疗患者的预防性抗真菌作用[J]. 上海交通大学学报（医学版），2022，42（6）：792-796.

JIN L，XU W B，YE C J，et al. Prophylactic antifungal effect of posaconazole on patients with hematological malignant tumor undergoing chemotherapy[J]. J Shanghai Jiao Tong Univ Med Sci，2022，42（6）：792-796.

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.

ZHANG F Y，ZHANG R X，SONG X W，et al. Research progress of influencing factors for plasma concentration of posaconazole[J]. Chin J Hosp Pharm，2021，41（9）：971-976.

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 R C，YU J，WANG Z Y，et al. Effect of posaconazole combined with proton pump inhibitors on blood concentrations and invasive fungal infection in patients with malignant hematological disorders[J]. China Pharm，2023，34（10）：1237-1241.

VAN DER ELST K C，BROUWERS C H，VAN DEN HEUVEL E R，et al. Subtherapeutic posaconazole exposure and treatment outcome in patients with invasive fungal disease[J]. Ther Drug Monit，2015，37（6）：766-771.

JOHN J，LOO A，MAZUR S，et al. Therapeutic drug monitoring of systemic antifungal agents：a pragmatic approach for adult and pediatric patients[J]. Expert Opin Drug Metab Toxicol，2019，15（11）：881-895.

DOLTON M J，BRÜGGEMANN R J，BURGER D M，et al. Understanding variability in posaconazole exposure using an integrated population pharmacokinetic analysis[J]. Antimicrob Agents Chemother，2014，58（11）：6879-6885.

SHU Y S，SHI Y P，YANG Y L，et al. Progress of triazole antifungal agent posaconazole in individualized therapy[J]. J Clin Pharm Ther，2022，47（12）：1966-1981.

国家药典委员会.中华人民共和国药典：四部[M].2020年版.北京：中国医药科技出版社，2020：466-472.

National Pharmacopoeia Commission. Chinese pharmacopoeia：part Ⅳ[M]. 2020 Edition. Beijing：China Medical Science Press，2020：466-472.

DE PAUW B，WALSH T J，DONNELLY J P，et al. Revised definitions of invasive fungal disease from the European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group（EORTC/MSG）Consensus Group[J]. Clin Infect Dis，2008，46（12）：1813-1821.

SEGAL B H，HERBRECHT R，STEVENS D A，et al. Defining responses to therapy and study outcomes in clinical trials of invasive fungal diseases：Mycoses Study Group and European Organization for Research and Treatment of Cancer consensus criteria[J]. Clin Infect Dis，2008，47（5）：674-683.

SHEN Y，HUANG X J，WANG J X，et al. Posaconazole vs. fluconazole as invasive fungal infection prophylaxis in China：a multicenter，randomized，open-label study[J]. Int J Clin Pharmacol Ther，2013，51（9）：738-745.

CORNELY O A，MAERTENS J，WINSTON D J，et al. Posaconazole vs. fluconazole or itraconazole prophylaxis in patients with neutropenia[J]. N Engl J Med，2007，356（4）：348-359.

DESPLANQUES P Y，BURLACU R，POINSIGNON V，et al. Factors influencing posaconazole plasmatic concentrations in patients presenting with acute myeloid leukemia[J]. Med Mal Infect，2014，44（4）：174-179.

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

MÄRTSON A G，VERINGA A，BAKKER M，et al. Posaconazole trough concentrations are not influenced by inflammation：a prospective study[J]. Int J Antimicrob Agents，2019，53（3）：325-329.

VEHRESCHILD J J，MÜLLER C，FAROWSKI F，et al. Factors influencing the pharmacokinetics of prophylactic posaconazole oral suspension in patients with acute mye-loid leukemia or myelodysplastic syndrome[J]. Eur J Clin Pharmacol，2012，68（6）：987-995.

MICELI M H，PERISSINOTTI A J，KAUFFMAN C A，et al. Serum posaconazole levels among haematological cancer patients taking extended release tablets is affected by body weight and diarrhoea：single centre retrospective analysis[J]. Mycoses，2015，58（7）：432-436.

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