title: Tolerance to oral H2-receptor antagonists.
abstract: The acid-inhibitory action of H2-receptor antagonists was shown to decrease after one to two weeks of dosing in healthy volunteers. This tolerance was evaluated in three randomized, placebo-controlled trials with the H2-receptor antagonists famotidine, 40 mg given after the evening meal for 28 days; ranitidine, 300 mg four times a day for seven days followed by 300 mg at night until day 28; and ranitidine, 300 mg three times a day vs 300 mg at night for 14 days. Continuous 24-hr pH monitoring with glass electrodes was performed under fed conditions. The median 24-hr pH decreased from 3.2 on day 1 with famotidine 40 mg to 1.9 on day 28 (P less than 0.0012). After seven days of dosing with ranitidine 300 mg four times a day the median 24-hr pH dropped from 5.0 on day 1 to 3.0 on day 7 (P less than 0.001) and then to 2.2 with ranitidine 300 mg at night on day 28. With ranitidine 300 mg three times a day the median 24-hr pH fell from 4.3 on day 1 to 2.4 on day 14 (P less than 0.0005). With ranitidine 300 mg at night the respective pH values were 2.5 and 1.8 (P less than 0.003). Tolerance to H2-receptor antagonists given in a single evening dose was only evident during the night, whereas tolerance occurred throughout the day and night with the three- and four-times-a-day regimens. A large increase in the interindividual variability of pH response was seen during the nighttime.
authors.affiliation: Department of Medicine, University of Berne, Inselspital, Switzerland.
authors.forename: C H
authors.initials: CH
authors.lastname: Wilder-Smith
authors.forename: T
authors.initials: T
authors.lastname: Ernst
authors.forename: M
authors.initials: M
authors.lastname: Gennoni
authors.forename: B
authors.initials: B
authors.lastname: Zeyen
authors.forename: F
authors.initials: F
authors.lastname: Halter
authors.forename: H S
authors.initials: HS
authors.lastname: Merki
mesh_terms: D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D002940:Circadian Rhythm / Q000187:drug effects / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004361:Drug Tolerance; D015738:Famotidine / Q000008:administration & dosage; D005260:Female; D005745:Gastric Acidity Determination; D005753:Gastric Mucosa / Q000187:drug effects / Q000378:metabolism; D006635:Histamine H2 Antagonists / Q000008:administration & dosage*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008297:Male; D010919:Placebos; D016032:Randomized Controlled Trials as Topic; D011899:Ranitidine / Q000008:administration & dosage; D012016:Reference Values; D013997:Time Factors
chemical_list: D006635:Histamine H2 Antagonists; D010919:Placebos; D015738:Famotidine; D011899:Ranitidine