Reliable acid suppression with pantoprazole contrasts with rapid development of tolerance to ranitidine in healthy individuals

Objectives: Development of tolerance (tachyphylaxis) has been observed duri ng treatment with H receptor antagonists, hut not with proton pump inhibito rs. In the present study, the time-course of acid inhibition during repeate d administration of pantoprazole was compared with that of ranitidine. Methods and Study Participants: 20 healthy individuals were included in an open, randomised, two-period, crossover study. Each participant received pa ntoprazole 40mg or ranitidine 300mg for 28 days and vice versa, separated b y a 28-day washout period. Intragastric 24-hour pH-metry as well as determi nation of serum gastrin levels were performed on days 1, 7 and 28 of each t reatment period. Results: Administration of pantoprazole led to an increase in median 24-hou r pH from 1.6 (baseline) to 2.5 on day 1. In the case of ranitidine, median 24-hour pH increased from 1.6 (baseline) to 2.4. However, on day 7 of rani tidine administration, development of tolerance was evident; the median 24- hour pH decreased to 2.0 and remained at 1.9 until the end of the study. In contrast, pantoprazole effectively inhibited acid secretion and achieved a constant pH-elevation until day 28 (pH 3.6 and 3.7 on days 7 and 28, respe ctively). On days 7 and 28, the median 24-hour pH was significantly higher with pantoprazole than with ranitidine (p < 0.001). Pharmacodynamic toleran ce was shown by a crossover analysis for ranitidine but not for pantoprazol e (p < 0.01). Following administration of either ranitidine or pantoprazole , serum gastrin levels were moderately elevated. Conclusion: Pantoprazole achieved a long-lasting inhibition of acid secreti on. while tolerance was observed with ranitidine within 7 days of administr ation.