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Pharmacodynamic effects of 3-day intravenous treatment with pantoprazole or ranitidine after 10 days of oral ranitidine.

Tachyphylaxis (drug tolerance) is an undesirable condition in drug therapy with histamine-2-receptor antagonists (H2RAs). The concept of overcoming tachyphylaxsis via intravenous (i.v.) administration of proton-pump inhibitors (PPIs) or H2RAs is of significant interest to physicians. In the present study, 32 healthy Helicobacter pylori negative male volunteers were evaluated for the ability of i.v. pantoprazole or i.v. ranitidine to overcome oral ranitidine tachyphylaxis. After 10 days of oral treatment with enteric-coated 300-mg ranitidine tablets once daily in the evening, two groups of 16 volunteers each were randomized to receive either i.v. pantoprazole or i.v. ranitidine for up to 72 h. The primary variable was defined as the increase in 24-h gastric pH median after 1 day of i.v. treatment; the secondary variable was median percentage of time that 24-h gastric pH was <4, as calculated by Hodges-Lehman shift estimators. After 10 days of oral ranitidine treatment, tachyphylaxis was present in all volunteers. Within 1 day of continuous i.v. pantoprazole or i.v. ranitidine administration, 24-h median gastric pH increased from pH 1.45 to pH 3.50 (241%) and from pH 1.50 to pH 2.35 (157%), respectively. I.v. pantoprazole was found to be significantly more effective (p<0.05) than i.v. ranitidine in increasing the 24-h gastric pH after oral ranitidine tachyphylaxis.