To address the limited bioavailability and intolerance of the conventional itraconazole formulations, a new formulation labelled SUBA-itraconazole (for SUper BioAvailability) has been developed, however the specific effect of food and gastric pH are unknown. This study evaluated the pharmacokinetic profile of SUBA-itraconazole under fasting and fed conditions, as well as with the concomitant administration of a proton pump inhibitor. The effect of food was assessed in an open-label, randomized, cross-over bioavailability study of SUBA-itraconazole capsules 65 mg (2 x 65 mg BID) in healthy adults (n = 20) under fasting and fed conditions to steady-state levels. Secondly, an open-label, two-treatment, fixed-sequence comparative bioavailability study in healthy adults (n=28) under fasted conditions compared the pharmacokinetics of a single oral dose of SUBA-itraconazole capsules (2 x 65 mg/day) with and without co-administration of daily omeprazole delayed-release capsules (1 x 40 mg/day) under steady-state conditions. In the fed and fasted state SUBA-itraconazole demonstrated similar concentrations at the end of the dosing interval, with modestly lower total and peak itraconazole (ITZ) exposure when administered under fed conditions compared to the fasted state; fed/fasted ratios of 78.09% (90%CI 74.49-81.86%) for AUCtau [14183.2 vs. 18479.8 hr·ng/mL], 73.05% (90%CI 69.01-77.33%) for Cmax,ss [1519.1 vs. 2085.2 ng/mL] and 91.53% (90%CI 86.41-96.96%) for Ctrough [1071.5 vs. 1218.5 ng/mL]. When dosed concomitantly with omeprazole there was a 22% increase in total plasma exposure of ITZ, as measured by AUC0- (p = 0.0069), and a 31% increase in peak plasma exposure of ITZ, as measured by Cmax (p = 0.0083).
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