Intravenous pentagastrin can induce the illusion of 'tolerance' to a single dose of an H2-blocker in man.

In a double-blind study of Latin square design, twelve healthy male subjects were dosed with combinations of ranitidine 300 mg or placebo (at 08.50 hours) and intravenous pentagastrin (0.6 microgram.kg/h) or 0.9% saline (07.00-18.00 hours). Breakfast and lunch were served at 08.15 and 13.15 hours, respectively; hourly intragastric acidity and plasma gastrin concentration were measured from 08.00-18.00 hours. During oral dosing with placebo, intravenous pentagastrin raised median 10-h integrated intragastric acidity (315 to 615 pmol.h/L; P less than 0.001) and lowered gastrin (86 to 55 mmol.h/L; P less than 0.001). During oral dosing with ranitidine 300 mg, compared with intravenous saline, the pentagastrin infusion returned acidity towards normal (67 to 293 pmol.h/L; P less than 0.001) and lowered gastrin (209 to 135 pmol.h/L; P less than 0.001). This study demonstrates that a continuous pentagastrin infusion can overcome H2-blockade and return intragastric acidity towards normal. Hypergastrinaemia observed during continued dosing with an H2-blocker may be the mechanism for the development of tolerance.

RCT Entities:   Population Interventions Outcomes