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Observational Study
. 2020 Aug;86(8):1661-1666.
doi: 10.1111/bcp.14267. Epub 2020 Mar 9.

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

Sara Blanco Dorado  1   2   3 , Olalla Maroñas Amigo  4   5 , Ana Latorre-Pellicer  4 , María Teresa Rodríguez Jato  1 , Ana López-Vizcaíno  6 , Aurea Gómez Márquez  7 , Belén Bardán García  8 , Dolores Belles Medall  9 , Gema Barbeito Castiñeiras  10 , María Luisa Pérez Del Molino Bernal  10 , Manuel Campos-Toimil  3 , Francisco Otero Espinar  3 , Andrés Blanco Hortas  11 , Irene Zarra Ferro  1   2 , Ángel Carracedo  4   5 , María Jesús Lamas  2 , Anxo Fernández-Ferreiro  1   2   3
Affiliations
Observational Study

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

Sara Blanco Dorado et al. Br J Clin Pharmacol. 2020 Aug.

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.

Keywords: cytochrome inhibition; drug interaction; proton-pump inhibitors; voriconazole.

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Figures

FIGURE 1
FIGURE 1
Box‐and‐whisker plots of voriconazole trough concentration in the 3 groups. The line inside the box, the lower and upper box ends, and the lower and upper whiskers represented the median value, the 25th and 75th percentiles, and the 5th and 95th percentiles of voriconazole trough concentration. Filled circles were outliers. Comparisons of the voriconazole trough concentration between the OME group and PAN groups were performed by the Mann–Whitney U test. PPI, proton‐pump inhibitor; OME, omeprazole; PAN, pantoprazole
FIGURE 2
FIGURE 2
Effect of concomitant medication of PPIs on the percentage of patients obtaining therapeutic, subtherapeutic or supratherapeutic voriconazole trough concentration. PPI, proton‐pump inhibitor; OME, omeprazole; PAN, pantoprazole
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