Single-Dose Crossover Comparative Bioavailability Study of Two Different Posaconazole 100 mg Gastro-Resistant Tablets Under Fasted and Fed Conditions in Healthy Volunteers.

Objective: This study aimed to compare the bioavailability of two different gastro-resistant oral tablet formulations of posaconazole under fasted and fed conditions and to evaluate a potential food effect on the bioavailability of each formulation.

Materials and methods: Healthy volunteers randomly assigned to receive a test product (Posagil^® 100 mg gastro-resistant tablet) or reference product (Noxafil^® 100 mg gastro-resistant tablet) were included in this single-center, randomized, four-period (days 1, 15, 29 and 43), four-sequence crossover comparative bioavailability study. Data on posaconazole plasma concentrations and related pharmacokinetic profile (the maximum observed plasma concentration [C_max] from time 0 to the time of last observed quantifiable plasma concentration [AUC_0-T] and from time zero to infinity [AUC_0-∞]) were recorded to evaluate efficacy of the test product in relation to the reference product under both fasted and fed conditions, based on bioequivalence (T-fasted vs. R-fasted and T-fed vs. R-fed) and food effect (T-fasted vs. T-fed and R-fasted vs. R-fed) assessments. Safety was evaluated through assessment of adverse events (AEs), standard laboratory evaluations, and vital signs.

Results: The bioequivalence criteria were met under fed conditions (T-fed vs. R-fed: geometric LSMean ratios of C_max, AUC_0-T, and AUC_0-∞ of posaconazole were 97.41%, 97.45%, and 97.08%, respectively; all within the range of 80% to 125%) but not under fasted conditions. There was a food effect on the reference product (R-fed vs. R-fasted: geometric LSMean ratios of C_max, AUC_0-T, and AUC_0-∞ of posaconazole were 145.32%, 138.84%, and 138.46%, respectively) but not on the test product. No safety concerns were identified.

Conclusions: Our findings suggest that the pharmacokinetic profile of Posagil^® is similar to the pharmacokinetic profile of Noxafil^®. The generic Posagil^® seems to have similarly high bioavailability under fed and fasted conditions, offering a higher posaconazole exposure than the original Noxafil^® in the fasted state. Hence, Posagil^® may be considered a value-added generic product that offers adequate posaconazole exposure under fasted state and fed state, regardless of the concomitant high-fat meal intake.