24-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 m an. Its effect on intragastric pH following single and repeated oral i ntake was investigated in comparison to omeprazole by continuous intra gastric pH-metry at doses recommended for treatment of peptic ulcer di sease. Methods: Sixteen healthy male subjects underwent two dosing per iods. From day 1 to day 7, they were given once daily by mouth 40 mg p antoprazole in one period and 20 mg omeprazole in the other period, ac cording to a double-blind randomized crossover design. Twenty-four-hou r intragastric pH was recorded and frequent blood samples for pharmaco kinetic analysis were taken on day 1 and day 7. A placebo pH profile w as obtained prior to each treatment period. Results: Pantoprazole was significantly more effective than omeprazole with regard to increase i n 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 adm inistration of both drugs markedly increased the effect on intragastri c pH. With pantoprazole, steady-state serum concentrations were obtain ed after the first dose, but not with omeprazole. Both drugs were well tolerated without relevant changes in vital signs of clinical laborat ory parameters. Conclusion: Pantoprazole 40 mg is significantly more e ffective than omeprazole 20 mg in raising intragastric pH.