The pharmacodynamics and pharmacokinetics of S‐tenatoprazole‐Na 30 mg, 60 mg and 90 mg vs. esomeprazole 40 mg in healthy male subjects

Aliment Pharmacol Ther 31, 648–657SummaryBackground  Racemic tenatoprazole 40 mg/day provides more prolonged acid suppression than esomeprazole 40 mg/day.Aim  To compare pharmacodynamic and pharmacokinetic profiles of tenatoprazole and esomeprazole.Methods  A single‐centre, double‐blind, double‐dummy, randomized, 4‐way, cross‐over study was conducted in 32 healthy male subjects. S‐tenatoprazole‐Na 30, 60 or 90 mg, or esomeprazole 40 mg was administered once daily for 5 days with 10‐day washout intervals. The 24‐h intragastric pH was recorded at baseline and on day 5 of each period.Results  On day 5, median pH (5.34 ± 0.45 and 5.19 ± 0.52 vs. 4.76 ± 0.82, respectively, P < 0.002) and percentage time with pH > 4 (80 ± 11 and 77 ± 12, vs. 63 ± 11 respectively, P < 0.0001) for 24‐h were higher with S‐tenatoprazole‐Na 90 mg and 60 mg than esomeprazole. In nocturnal periods, S‐tenatoprazole‐Na 90 mg, 60 mg and 30 mg were superior to esomeprazole with regard to median pH (5.14 ± 0.64, 4.94 ± 0.65, 4.65 ± 0.86 and 3.69 ± 1.18 respectively, P < 0.0001) and percentage time with pH > 4 (77 ± 12, 73 ± 17, 64 ± 17 and 46 ± 17 respectively, P < 0.0001). Proportion of subjects with nocturnal acid breakthrough with S‐tenatoprazole‐Na 90 mg, 60 mg and 30 mg was significantly less than with esomeprazole (54.8, 43.3, 56.7 and 90.3 respectively, P < 0.04). The proportion of subjects with >16 hrs with pH >4 was significantly higher with S‐tenatoprazole‐Na 90 mg and 60 mg than with esomeprazole (87.1%, 83.3% and 41.9% respectively, P < 0.02).Conclusions  S‐tenatoprazole‐Na produced significantly greater and more prolonged dose‐dependent 24‐h and nocturnal acid suppression than esomeprazole. S‐tenatoprazole‐Na may provide greater clinical efficacy compared with current PPIs for patients with ineffective once‐daily therapy.