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

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.

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

Publication types

  • Multicenter Study
  • Observational Study

MeSH terms

  • 2-Pyridinylmethylsulfinylbenzimidazoles
  • Drug Interactions
  • Enzyme Inhibitors
  • Esomeprazole
  • Humans
  • Omeprazole / therapeutic use*
  • Pantoprazole / therapeutic use*
  • Prospective Studies
  • Proton Pump Inhibitors / therapeutic use*
  • Voriconazole / blood*

Substances

  • 2-Pyridinylmethylsulfinylbenzimidazoles
  • Enzyme Inhibitors
  • Proton Pump Inhibitors
  • Pantoprazole
  • Voriconazole
  • Omeprazole
  • Esomeprazole