Twenty-four-hour intragastric pH profiles and pharmacokinetics following single and repeated oral administration of the proton pump inhibitor pantoprazole in comparison to omeprazole.
BACKGROUND
Pantoprazole is a proton pump inhibitor characterized by a low potential to interact with the cytochrome P450 enzyme system in man. Its effect on intragastric pH following single and repeated oral intake was investigated in comparison to omeprazole by continuous intragastric pH-metry at doses recommended for treatment of peptic ulcer disease.


METHODS
Sixteen healthy male subjects underwent two dosing periods. From day 1 to day 7, they were given once daily by mouth 40 mg pantoprazole in one period and 20 mg omeprazole in the other period, according to a double-blind randomized crossover design. Twenty-four-hour intragastric pH was recorded and frequent blood samples for pharmacokinetic analysis were taken on day 1 and day 7. A placebo pH profile was obtained prior to each treatment period.


RESULTS
Pantoprazole was significantly more effective than omeprazole with regard to increase in 24-h and daytime pH, following both single (median 24-h pH: 1.45 vs. 1.3, P < 0.05; median daytime pH: 1.6 vs. 1.3, P < 0.01) and repeated (median 24-h pH: 3.15 vs. 2.05, P < 0.01; median daytime pH: 3.8 vs. 2.65, P < 0.05) oral intake. As compared to the first dose, repeated administration of both drugs markedly increased the effect on intragastric pH. With pantoprazole, steady-state serum concentrations were obtained after the first dose, but not with omeprazole. Both drugs were well tolerated without relevant changes in vital signs of clinical laboratory parameters.


CONCLUSIONS
Pantoprazole 40 mg is significantly more effective than omeprazole 20 mg in raising intragastric pH.
Hartmann
M
M
Byk Gulden Pharmaceuticals, Konstanz, Germany.
Theiss
U
U
Huber
R
R
Lühmann
R
R
Bliesath
H
H
Wurst
W
W
Lücker
P W
PW
D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D000328:Adult; D019540:Area Under Curve; D001562:Benzimidazoles / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology*; D002940:Circadian Rhythm / Q000187:drug effects / Q000502:physiology*; D018592:Cross-Over Studies; D004032:Diet; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology*; D005744:Gastric Acid / Q000378:metabolism*; D005745:Gastric Acidity Determination; D006207:Half-Life; D006801:Humans; D008297:Male; D009853:Omeprazole / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology*; D000077402:Pantoprazole; D054328:Proton Pump Inhibitors; D013454:Sulfoxides / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology*
D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D001562:Benzimidazoles; D004791:Enzyme Inhibitors; D054328:Proton Pump Inhibitors; D013454:Sulfoxides; D000077402:Pantoprazole; D009853:Omeprazole