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感染是否会改变抗真菌药物的分布:一项探索药代动力学变化的动物模型研究。

Does infection alter antifungal distribution: an animal model exploring pharmacokinetic changes.

作者信息

Alves Izabel Almeida, Staudt Keli Jaqueline, Torres Bruna Gaelzer Silva, Oliveira Calinca Elioterio, Rieper Ryan Lago Araujo, Kowalski Layza, de Araújo Bibiana Verlindo

机构信息

Faculdade de Farmácia, Departamento do Medicamento, Universidade Federal da Bahia, Salvador, Bahia, Brasil.

Programa de Pós-Graduação em Farmácia, Universidade Estadual da Bahia, Salvador, Bahia, Brasil.

出版信息

Future Microbiol. 2025 Apr;20(6):489-498. doi: 10.1080/17460913.2025.2484956. Epub 2025 Apr 3.

DOI:10.1080/17460913.2025.2484956
PMID:40178503
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11980448/
Abstract

AIM

Assessing the disseminated meningitis caused by in Wistar rats and its impact on antifungal distribution by microdialysis (µD).

MATERIALS & METHODS: The yeast presence was investigated in different tissues by histological and microbiological assays, and biochemical parameters such as urea, glutamate oxaloacetate transaminase (GOT), glutamate pyruvate transaminase (GPT), creatinine, creatine kinase (CK), creatinine, albumin level, leukocyte counts, and brain vascular permeability (Evans blue test) were evaluated in healthy and infected groups. Levels of fluconazole reached in the animal's brain were determined by µD.

RESULTS

Differences in albumin, urea, GPT, and CK between healthy and infected animals were observed in the levels of Evans blue as well as in the brain (0.51 1.50 µg/g). The drugs' distribution in the brain of infected animals was higher than that in the brain of healthy ones (ft = 1.37 ft = 0.54).

CONCLUSION

The model validated presents characteristics similar to those observed in patients and can be applied to pharmacokinetic investigations.

摘要

目的

评估Wistar大鼠中由[未提及具体病原体]引起的播散性脑膜炎及其对通过微透析(µD)进行的抗真菌药物分布的影响。

材料与方法

通过组织学和微生物学检测在不同组织中研究酵母的存在情况,并在健康组和感染组中评估生化参数,如尿素、谷草转氨酶(GOT)、谷丙转氨酶(GPT)、肌酐、肌酸激酶(CK)、肌酐、白蛋白水平、白细胞计数以及脑血管通透性(伊文思蓝试验)。通过微透析确定动物脑中氟康唑的水平。

结果

在伊文思蓝水平以及脑中(0.51±1.50 µg/g)观察到健康动物和感染动物在白蛋白、尿素、GPT和CK方面存在差异。感染动物脑中药物的分布高于健康动物脑中的分布(ft = 1.37,ft = 0.54)。

结论

经验证的该模型具有与在患者中观察到的特征相似的特点,可应用于药代动力学研究。

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