Intravenous pentagastrin can induce the illusion of ‘tolerance’ to a single dose of an H2‐blocker in man

SUMMARY 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 µg. 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 < 0.001) and lowered gastrin (86 to 55 mmol. h/L; P < 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 < 0.001) and lowered gastrin (209 to 135 pmol. h/L; P < 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‐blocket may be the mechanism for the development of tolerance.