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一项评估质子泵抑制剂奥美拉唑和泮托拉唑对伏立康唑血药浓度影响的多中心前瞻性研究。

A multicentre prospective study evaluating the impact of proton-pump inhibitors omeprazole and pantoprazole on voriconazole plasma concentrations.

作者信息

Blanco Dorado Sara, Maroñas Amigo Olalla, Latorre-Pellicer Ana, Rodríguez Jato María Teresa, López-Vizcaíno Ana, Gómez Márquez Aurea, Bardán García Belén, Belles Medall Dolores, Barbeito Castiñeiras Gema, Pérez Del Molino Bernal María Luisa, Campos-Toimil Manuel, Otero Espinar Francisco, Blanco Hortas Andrés, Zarra Ferro Irene, Carracedo Ángel, Lamas María Jesús, Fernández-Ferreiro Anxo

机构信息

Pharmacy Department, University Clinical Hospital Santiago de Compostela, Santiago de Compostela, Spain.

Clinical Pharmacology Group, University Clinical Hospital, Health Research Institute of Santiago de Compostela, Santiago de Compostela, Spain.

出版信息

Br J Clin Pharmacol. 2020 Aug;86(8):1661-1666. doi: 10.1111/bcp.14267. Epub 2020 Mar 9.

Abstract

Voriconazole is an antifungal metabolised by CYP2C19 enzyme, which can be inhibited by proton-pump inhibitors (PPIs). A prospective observational study was carried out to determine the influence of PPIs on voriconazole pharmacokinetic. The 78 patients included were divided into 4 groups: omeprazole (n = 32), pantoprazole (n = 25), esomeprazole (n = 3) and no PPI (n = 18). Patients with no PPI had no significant difference in plasma voriconazole concentration when compared with those with PPI (2.63 ± 2.13 μg/mL [95% confidence interval {CI} 1.57-3.69] vs 2.11 ± 1.73 μg/mL [95%CI 1.67-2.55], P > .05). However, voriconazole plasma concentration was significantly lower in patients treated with pantoprazole vs those treated with omeprazole (1.44 ± 1.22 μg/mL [95%CI 0.94-1.94) vs 2.67 ± 1.88 μg/mL [95%CI 2.02-3.32], P = .013) suggesting a greater CYP2C19 enzyme inhibitory effect of omeprazole. This study demonstrates the greater CYP inhibition capacity of omeprazole and should be helpful for the choice of PPIs for patients treated with voriconazole.

摘要

伏立康唑是一种由CYP2C19酶代谢的抗真菌药物,质子泵抑制剂(PPI)可抑制该酶。开展了一项前瞻性观察性研究,以确定PPI对伏立康唑药代动力学的影响。纳入的78例患者被分为4组:奥美拉唑组(n = 32)、泮托拉唑组(n = 25)、埃索美拉唑组(n = 3)和未使用PPI组(n = 18)。与使用PPI的患者相比,未使用PPI的患者血浆伏立康唑浓度无显著差异(2.63±2.13μg/mL[95%置信区间{CI}1.57 - 3.69] vs 2.11±1.73μg/mL[95%CI 1.67 - 2.55],P>.05)。然而,泮托拉唑治疗的患者与奥美拉唑治疗的患者相比,伏立康唑血浆浓度显著更低(1.44±1.22μg/mL[95%CI 0.94 - 1.94] vs 2.67±1.88μg/mL[95%CI 2.02 - 3.32],P =.013),提示奥美拉唑对CYP2C19酶的抑制作用更强。本研究证明了奥美拉唑具有更强的CYP抑制能力,并应有助于为接受伏立康唑治疗的患者选择PPI。

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