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 (R) 100 mg gastro-resistant tablet) or reference product (Noxafil (R) 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-infinity)]) 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-infinity) 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-infinity) 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 (R) is similar to the pharmacokinetic profile of Noxafil (R). The generic Posagil (R) seems to have similarly high bioavailability under fed and fasted conditions, offering a higher posaconazole exposure than the original Noxafil (R) in the fasted state. Hence, Posagil (R) 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.