Pharmacokinetics.
RESIDUAL
Plasma TBP concentrations were quantifiable by the first post dose sample time (0.25 h) for all subjects following TBP-PI-HBr alone (Treatment A) or in combination with omeprazole once daily (QD) (Treatment C), and for 12 out of 20 profiles following TBP-PI-HBr combined with aluminum hydroxide/magnesium hydroxide/simethicone (Treatment B). Mean peak TBP concentrations (Cmax) were lower (7.4, 10.1 μg/mL) for combination treatments relative to TBP-PI-HBr administered alone (12.9 μg/mL), occurring at 0.75 h post dose following TBP-PI-HBr alone or in combination with aluminum hydroxide/magnesium hydroxide/simethicone, and at 1 h post dose following TBP-PI-HBr combined with omeprazole QD, respectively (TBP mean (standard deviation) plasma concentration-time profile following a 600 mg dose of TBP-PI-HBr alone (Treatment A) and combined with aluminum hydroxide/magnesium hydroxide/simethicone (Treatment B) or omeprazole (Treatment C) in healthy subjects (linear top, semi-log bottom).The median and range of individual TPharmacokinetic parameters for each treatment groupTreatment A: 600 mg (2 × 300 mg tablets) TBP-PI-HBr administered at Hour 0 on Day 1.Treatment B: 20 mL Mylanta Maximum Strength Classic Flavor (800 mg aluminum hydroxide/800 mg magnesium hydroxide/80 mg simethicone per 10 mL) oral suspension with 600 mg (2 × 300 mg tablets) TBP-PI-HBr at Hour 0 on Day 1.Treatment C: 40 mg (1 × 40 mg capsule) omeprazole administered QD at Hour -2 on Days 1 through 5, with 600 mg (2 × 300 mg tablets) TBP-PI-HBr administered at Hour 0 on Day 5.AUCs and Cmax are presented as geometric mean (geometric CV%).TtBased on the statistical comparisons of natural log (ln)-transformed TBP AUCStatistical comparisons of plasma PK parameters for TBP + aluminum hydroxide/magnesium hydroxide/simethicone versus TBP alone and TBP + omeprazole versus TBP alone (PK population)Treatment B: 20 mL maximum strength classic flavor (800 mg aluminum hydroxide/800 mg magnesium hydroxide/80 mg simethicone per 10 mL) oral suspension with 600 mg (2 × 300 mg tablets) TBP-PI-HBr at Hour 0 on Day 1.Treatment A: 600 mg (2 × 300 mg tablets) TBP-PI-HBr administered at hour 0 on day 1.Parameters were ln-transformed prior to analysis.Geometric least-squares means (LSMs) were calculated by exponentiating the LSMs derived from the ANOVA.Geometric Mean Ratio (GMR) = 100 × (test/reference).Intra-subject CV% was calculated as 100 × square root(exp[MSE]-1), where MSE = Residual variance from ANOVA.Treatment C: 40 mg (1 × 40 mg capsule) omeprazole administered QD at Hour -2 on Days 1 through 5, with 600 mg (2 × 300 mg tablets) TBP-PI-HBr administered at Hour 0 on Day 5.Similarly, based on the statistical comparisons of ln-transformed TBP AUC