Intra-oesophageal pH profiles and pharmacokinetics of pantoprazole and esomeprazole: a crossover study in patients with gastro-oesophageal reflux disease.
OBJECTIVE
To compare the effect of pantoprazole and esomeprazole on intra-oesophageal pH and investigate their pharmacokinetics in patients with symptomatic gastro-oesophageal reflux disease (GORD).


METHODS
Double-blind, randomized, two-period crossover study. Caucasian men with symptomatic GORD (n=48) were selected on the basis of clinical records of typical GORD symptoms, confirmed by a pathological reflux time (oesophageal pH<4 for > or =6% of the time). They received oral pantoprazole 40 mg once daily (od) or esomeprazole 40 mg od for seven days. Continuous 24 h oesophageal pH-metry was performed at baseline and day 7. Evaluations included: pre- and post-treatment differences in the percentage of time with pH<4.0 and <3.0 between baseline and day 7; area under the curve (AUC), Cmax, and T(1/2); point estimates and 90% confidence intervals (CI) on days 1 and 7, calculated for ratios of the AUC and Cmax.


RESULTS
Both drugs decreased the mean total number of reflux episodes and reduced the percentage of reflux time within 24 h to <3%. No pathological reflux was detectable after repeated administration of either drug. The 90% CI were within the predefined range at all time points; thus, equivalence of pantoprazole and esomeprazole was concluded. For pantoprazole, Cmax and AUC were unchanged on day 7 vs day 1, confirming its high and constant bioavailability. For esomeprazole, Cmax and AUC were increased on day 7 vs day 1 by 80% and 50%, respectively, indicating low initial bioavailability. No clinically relevant side effects were seen for either drug.


CONCLUSIONS
Pantoprazole and esomeprazole have equivalent effect on oesophageal pH, since no pathological reflux was detected after treatment with either drug. For esomeprazole, the Cmax and AUC increased after multiple dosing; for pantoprazole the pharmacokinetics were predictable and independent of the number of administered doses.
Simon
Bernd
B
IFE Institut für Forschung und Entwicklung, Witten, Germany.
Müller
Peter
P
Pascu
Oliviu
O
Gatz
Gudrun
G
Sander
Peter
P
Huber
Reinhard
R
Mascher
Hermann
H
D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D000328:Adult; D000897:Anti-Ulcer Agents / Q000097:blood / Q000627:therapeutic use*; D001562:Benzimidazoles / Q000097:blood / Q000627:therapeutic use*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D064098:Esomeprazole / Q000097:blood / Q000627:therapeutic use*; D004947:Esophagus / Q000378:metabolism; D005764:Gastroesophageal Reflux / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism; D006801:Humans; D006863:Hydrogen-Ion Concentration / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D000077402:Pantoprazole; D013454:Sulfoxides / Q000097:blood / Q000627:therapeutic use*
D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D000897:Anti-Ulcer Agents; D001562:Benzimidazoles; D013454:Sulfoxides; D000077402:Pantoprazole; D064098:Esomeprazole