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血液系统恶性肿瘤伴发热性中性粒细胞减少症患者万古霉素药代动力学参数的改变:贝叶斯软件估计

Altered Pharmacokinetics Parameters of Vancomycin in Patients with Hematological Malignancy with Febrile Neutropenia, a Bayesian Software Estimation.

作者信息

Alzahrani Abdullah M, Naeem Anjum, AlAzmi Aeshah, Hakami Alqassem Y, Karim Shahid, Ali Ahmed S, Kamel Fatemah Omer, Alzhrani Rami M, Alkhaldi Teaf S, Maghrabi Loujayne A, Alshehri Norah F, Alzahrani Yahya A

机构信息

Pharmaceutical Care Department, Ministry of National Guard-Health Affairs, Jeddah 22384, Saudi Arabia.

King Abdullah International Medical Research Center, Jeddah 21423, Saudi Arabia.

出版信息

Antibiotics (Basel). 2023 May 29;12(6):979. doi: 10.3390/antibiotics12060979.

DOI:10.3390/antibiotics12060979
PMID:37370298
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10295334/
Abstract

The pharmacokinetics of vancomycin vary significantly between specific groups of patients, such as critically ill patients and patients with hematological malignancy (HM) with febrile neutropenia (FN). Recent evidence suggests that the use of the usual standard dose of antibiotics in patients with FN may not offer adequate exposure due to pharmacokinetic variability (PK). Therefore, the purpose of this study is to assess the effect of FN on AUC as a key parameter for vancomycin monitoring, as well as to determine which vancomycin PK parameters are affected by the presence of FN using Bayesian software PrecisePK in HM with FN. This study was carried out in King Abdulaziz Medical City. All adult patients who were admitted to the Princess Norah Oncology Center PNOC between 1 January and 2017 and 31 December 2020, hospitalized and received vancomycin with a steady-state trough concentration measured before the fourth dose, were included. During the trial period, 297 patients received vancomycin during their stay at the oncology center, 217 of them meeting the inclusion criteria. Pharmacokinetic parameters were estimated for the neutropenic and non-FN patients using the precise PK Bayesian platform. The result showed that there was a significant difference ( < 0.05) in vancomycin clearance Cl, the volume of distribution at a steady-state V, the volume of distribution for peripheral compartment V, half-life for the elimination phase t½, and the first-order rate constant for the elimination process β in FN compared to non-FN patients. Furthermore, AUC was lower for FN patients compared to non-FN patients, < 0.05. FN has a significant effect on the PK parameters of vancomycin and AUC, which may require specific consideration during the treatment initiation.

摘要

万古霉素的药代动力学在特定患者群体之间存在显著差异,如重症患者以及患有血液系统恶性肿瘤(HM)并伴有发热性中性粒细胞减少症(FN)的患者。最近的证据表明,由于药代动力学变异性(PK),在FN患者中使用常规标准剂量的抗生素可能无法提供足够的药物暴露。因此,本研究的目的是评估FN对作为万古霉素监测关键参数的AUC的影响,并使用贝叶斯软件PrecisePK确定在患有FN的HM患者中,哪些万古霉素PK参数会受到FN的影响。本研究在阿卜杜勒阿齐兹国王医疗城进行。纳入了2017年1月1日至2020年12月31日期间入住诺拉公主肿瘤中心(PNOC)、住院并接受万古霉素治疗且在第四次给药前测量了稳态谷浓度的所有成年患者。在试验期间,297名患者在肿瘤中心住院期间接受了万古霉素治疗,其中217名符合纳入标准。使用精确PK贝叶斯平台估计中性粒细胞减少和非FN患者的药代动力学参数。结果显示,与非FN患者相比,FN患者的万古霉素清除率Cl、稳态分布容积V、外周室分布容积V、消除相半衰期t½以及消除过程的一级速率常数β存在显著差异(<0.05)。此外,与非FN患者相比,FN患者的AUC较低,<0.05。FN对万古霉素的PK参数和AUC有显著影响,在治疗开始时可能需要特别考虑。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5f10/10295334/a5b39ec166a7/antibiotics-12-00979-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5f10/10295334/f39166537075/antibiotics-12-00979-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5f10/10295334/9bfba6e06e74/antibiotics-12-00979-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5f10/10295334/47ac91092c7f/antibiotics-12-00979-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5f10/10295334/f32fb7e1b246/antibiotics-12-00979-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5f10/10295334/a5b39ec166a7/antibiotics-12-00979-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5f10/10295334/f39166537075/antibiotics-12-00979-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5f10/10295334/9bfba6e06e74/antibiotics-12-00979-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5f10/10295334/47ac91092c7f/antibiotics-12-00979-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5f10/10295334/f32fb7e1b246/antibiotics-12-00979-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5f10/10295334/a5b39ec166a7/antibiotics-12-00979-g005.jpg

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Microorganisms. 2023 Feb 24;11(3):567. doi: 10.3390/microorganisms11030567.
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