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泊沙康唑在侵袭性真菌感染成年患者中的药代动力学评估。

Evaluation of Posaconazole Pharmacokinetics in Adult Patients with Invasive Fungal Infection.

作者信息

Allegra Sarah, Fatiguso Giovanna, De Francia Silvia, Favata Fabio, Pirro Elisa, Carcieri Chiara, De Nicolò Amedeo, Cusato Jessica, Di Perri Giovanni, D'Avolio Antonio

机构信息

Department of Medical Sciences, Unit of Infectious Diseases, University of Torino, ASL Città di Torino, Amedeo di Savoia Hospital, Corso Svizzera 164, 10149 Turin, Italy.

Department of Biological and Clinical Sciences, University of Turin, S. Luigi Gonzaga Hospital, 10043 Orbassano (TO), Italy.

出版信息

Biomedicines. 2017 Nov 20;5(4):66. doi: 10.3390/biomedicines5040066.

Abstract

Mortality and morbidity due to invasive fungal infections have increased over the years. Posaconazole is a second-generation triazole agent with an extended spectrum of activity, which shows a high interindividual variability in its plasma levels, rendering dosing in many patients inconsistent or inadequate. Hence, posaconazole therapeutic drug monitoring, which is easily available in clinical practice, may improve treatment success and safety. The aim of the study was to describe posaconazole pharmacokinetics, and to evaluate the utility of therapeutic drug monitoring for therapy and prophylaxis in a cohort of adult patients. A fully validated chromatographic method was used to quantify posaconazole concentration in plasma collected from adult patients at the end of the dosing interval. Associations between variables were tested using the Pearson test. The Mann-Whitney test was used to probe the influence of categorical variables on continuous ones. A high inter-individual variability was shown. Of the 172 enrolled patients, among those receiving the drug by the oral route ( = 170), gender significantly influenced drug exposure: males showed greater posaconazole concentration than females ( = 0.028). This study highlights the importance of therapeutic drug monitoring in those with invasive fungal infections and its significant clinical implications; moreover we propose, for the first time, the possible influence of gender on posaconazole exposure.

摘要

多年来,侵袭性真菌感染导致的死亡率和发病率有所上升。泊沙康唑是一种第二代三唑类药物,抗菌谱更广,但其血药浓度存在较大个体差异,导致许多患者的给药剂量不一致或不足。因此,临床实践中易于开展的泊沙康唑治疗药物监测可能会提高治疗成功率和安全性。本研究的目的是描述泊沙康唑的药代动力学,并评估治疗药物监测在一组成年患者治疗和预防中的作用。采用一种经过充分验证的色谱方法,对成年患者给药间隔结束时采集的血浆中泊沙康唑浓度进行定量分析。变量之间的相关性采用Pearson检验进行分析。采用Mann-Whitney检验探究分类变量对连续变量的影响。结果显示个体间存在较大差异。在172名入组患者中,口服给药的患者(n = 170)中,性别对药物暴露有显著影响:男性的泊沙康唑浓度高于女性(P = 0.028)。本研究强调了治疗药物监测在侵袭性真菌感染患者中的重要性及其显著的临床意义;此外,我们首次提出性别可能对泊沙康唑暴露产生影响。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c568/5744090/78122781be11/biomedicines-05-00066-g001.jpg

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