Tolerance to famotidine and ranitidine treatment after 14 days of administration in healthy subjects without Helicobacter pylori infection

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Abstract
Background and Aim: The attenuated antisecretory activity observed during continuous administration of ranitidine has been described as tolerance. However, it remains unclear whether a similar phenomenon occurs with other histamine H2 receptor antagonists (H2RA). We investigated whether tolerance to famotidine, a stronger H2RA than ranitidine, occurs during long‐term administration.Methods: Seven healthy male Japanese subjects without Helicobacter pylori infection participated in a randomized cross‐over study in which ranitidine and famotidine were administered for 14 days with a 4‐week wash‐out period. We performed 24‐h intragastric pH monitoring on the first and 14th days of administration of each drug, and measured serum gastrin and plasma drug concentrations on the first, seventh and 14th days.Results: The acid‐inhibiting activity of ranitidine and famotidine declined during continuous administration. In particular, the potent nocturnal pH‐increasing effect of the H2RA, which was observed on day 1, declined on day 14. Serum gastrin concentrations on day 14 were significantly lower than those on day 7, although plasma drug concentrations remained unchanged.Conclusion: Tolerance to famotidine occurs during continuous administration for 14 days, as previously shown in ranitidine studies.