The pharmacodynamics and pharmacokinetics of S-tenatoprazole-Na 30 mg, 60 mg and
90 mg vs. esomeprazole 40 mg in healthy male subjects.
Author(s): Hunt RH, Armstrong D, Yaghoobi M, James C.
Affiliation(s): Farncombe Family Digestive Disease Research Institute, Division of
Gastroenterology, McMaster University & Hamilton Health Sciences, Hamilton, ON,
Canada. huntr@mcmaster.ca
Publication date & source: 2010, Aliment Pharmacol Ther. , 31(6):648-57
BACKGROUND: 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.
|