title: Intravenous pentagastrin can induce the illusion of 'tolerance' to a single dose of an H2-blocker in man.
abstract: 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.
authors.affiliation: Academic Department of Medicine, Royal Free Hospital School of Medicine, London, UK.
authors.forename: C U
authors.initials: CU
authors.lastname: Nwokolo
authors.forename: A
authors.initials: A
authors.lastname: Sawyerr
authors.forename: J T
authors.initials: JT
authors.lastname: Smith
authors.forename: R E
authors.initials: RE
authors.lastname: Pounder
mesh_terms: D000328:Adult; D004311:Double-Blind Method; D004361:Drug Tolerance; D005744:Gastric Acid / Q000378:metabolism*; D006635:Histamine H2 Antagonists / Q000494:pharmacology*; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D010418:Pentagastrin / Q000008:administration & dosage / Q000494:pharmacology*; D011899:Ranitidine / Q000494:pharmacology
chemical_list: D006635:Histamine H2 Antagonists; D011899:Ranitidine; D010418:Pentagastrin