Can changing an antifungal medicine from a liquid to a tablet make its absorption less dependent on food?

Details

Posaconazole oral suspension is a marketed extended-spectrum triazole with proven efficacy for antifungal treatment and prevention, and should be taken with food to maximize absorption. New tablet and capsule formulations were developed to optimize absorption and bioavailability.

This exploratory open-label, partially randomized, 2-part, 4-way, single-dose crossover study involved 16 healthy adults. It aimed to characterize the pharmacokinetics of posaconazole tablets and a capsule relative to the oral suspension under fasted and fed conditions, and to assess safety and tolerability.

Under fasted conditions, drug exposure—measured as the area under the concentration–time curve from time zero to infinity, AUC(0–∞)—was similar for the tablets and capsule: mean values were 11,700 ng · h/ml for tablet A (coefficient of variation [CV], 26%), 11,300 ng · h/ml for tablet B (CV, 22%), and 11,000 ng · h/ml for the capsule (CV, 25%). These exposures were substantially higher than the oral suspension's mean of 3,420 ng · h/ml (CV, 44%). The tablets and capsule showed less variability in exposure than the oral suspension.

Under fed conditions, the tablets and capsule again produced similar mean AUC(0–∞) values: 11,900 ng · h/ml for tablet A (CV, 23%), 12,400 ng · h/ml for tablet B (CV, 25%), and 12,300 ng · h/ml for the capsule (CV, 28%). Their exposure was slightly higher than that of the oral suspension, whose mean AUC(0–∞) was 8,750 ng · h/ml (CV, 24%).

Median times to maximum plasma drug concentration were 4 to 5 hours under fasted conditions and 6 to 8 hours under fed conditions. Mean half-lives were similar across all formulations under both conditions, ranging from 23.1 to 29.2 hours.

Consistent with previous data, exposure from the oral suspension increased 2.5- to 3-fold when given with a high-fat meal. Conversely, exposure from the tablets and capsule was not markedly affected by food. All posaconazole formulations at 100 mg were safe and well tolerated.