UHPLC method for simultaneous assessment of pharmacokinetic parameters of co-administered voriconazole and omeprazole using rat plasma

Abstract

Voriconazole (VRC) is a first-line therapeutic agent for the treatment of invasive fungal infections, whereas omeprazole (OMZ) is a commonly used acid suppressant; however, the two drugs are often used in combination in clinical practice. The aim of this research was to investigate how the co-administration of OMZ and VRC affects the pharmacokinetic characteristics of VRC in rats. A new ultra high-performance liquid chromatography (UHPLC) analytical method was developed and validated for simultaneous analysis of co-administered drugs using VRC and OMZ. A Shim-pack GIST-HP C18 column with 0.1 M triethylamine:acetonitrile (70:30, v/v) as the mobile phase (flow rate: 0.3 mL/min) was used, and UV detection was performed at 240 nm. Liquid–liquid extraction of plasma samples was carried out using dichloromethane. The bioanalytical method was linear over a range of VRC concentrations (100–2000 ng/mL) and OMZ (50–10,000 ng/mL) concentrations, and exhibited both accuracy and precision within the acceptable respective ranges. The average extraction recoveries for VRC and OMZ in plasma were 94.88 % and 82.76 %, respectively. Additionally, the method was successfully applied in vivo to estimate the pharmacokinetic features of VRC in the plasma of rats receiving gavage with low and high doses of OMZ. In conclusion, using a new UHPLC method, we determined that co-administration of OMZ substantially decreased the bioavailability of VRC in rats. Potentially significant drug interactions should be considered in patients receiving the combination of OMZ and VRC.