Twenty-four-hour intragastric pH

Tolerance within 5 days of continuous ranitidine administration

Leonard Lachman, Colin Howden

Research output: Contribution to journalArticle

68 Citations (Scopus)

Abstract

OBJECTIVE: To investigate further the phenomenon of pharmacological tolerance to H2-receptor antagonists, we undertook a study of the antisecretory effect of ranitidine with continuous daily administration. METHODS: A total of 28 healthy male volunteers were given ranitidine 150 mg q.i.d. for 5 days. Twenty-four-hour intragastric pH monitoring was performed predosing and on days 1 and 5 of ranitidine administration. Serial blood samples were collected on days 1 and 5 of ranitidine administration for pharmacokinetics. RESULTS: Mean 24-h intragastric pH was 2.62 predosing, 4.22 on day 1 of ranitidine administration and 3.28 on day 5 (p = 0.001, ranitidine day 1 vs day 5). Intragastric pH was >3, 4, and 5 for 69.9%, 54.3%, and 35.9%, respectively, on day 1 of ranitidine administration and was 45.8%, 30.1%, and 20.8% on day 5 (p < 0.005 for each comparison). Subjects' Helicobacter pylori status did not affect the antisecretory effect of ranitidine. There was no alteration in ranitidine pharmacokinetics to account for its reduced antisecretory effect. CONCLUSION: This study has demonstrated a statistically significant reduction in the antisecretory effect of ranitidine within 5 days of continuous administration which is not explained by altered ranitidine pharmacokinetics. This is further evidence for the development of a form of pharmacological tolerance to an H2-receptor antagonist within a few days of continuous daily dosing.

Original languageEnglish (US)
Pages (from-to)57-61
Number of pages5
JournalAmerican Journal of Gastroenterology
Volume95
Issue number1
DOIs
StatePublished - Jan 1 2000

Fingerprint

Ranitidine
Histamine H2 Receptors
Pharmacokinetics
Helicobacter pylori
Healthy Volunteers
Pharmacology

All Science Journal Classification (ASJC) codes

  • Hepatology
  • Gastroenterology

Cite this

Twenty-four-hour intragastric pH : Tolerance within 5 days of continuous ranitidine administration. / Lachman, Leonard; Howden, Colin.

In: American Journal of Gastroenterology, Vol. 95, No. 1, 01.01.2000, p. 57-61.

Research output: Contribution to journalArticle

@article{5b1db327c6fc430995f37a44008c0fc6,
title = "Twenty-four-hour intragastric pH: Tolerance within 5 days of continuous ranitidine administration",
abstract = "OBJECTIVE: To investigate further the phenomenon of pharmacological tolerance to H2-receptor antagonists, we undertook a study of the antisecretory effect of ranitidine with continuous daily administration. METHODS: A total of 28 healthy male volunteers were given ranitidine 150 mg q.i.d. for 5 days. Twenty-four-hour intragastric pH monitoring was performed predosing and on days 1 and 5 of ranitidine administration. Serial blood samples were collected on days 1 and 5 of ranitidine administration for pharmacokinetics. RESULTS: Mean 24-h intragastric pH was 2.62 predosing, 4.22 on day 1 of ranitidine administration and 3.28 on day 5 (p = 0.001, ranitidine day 1 vs day 5). Intragastric pH was >3, 4, and 5 for 69.9{\%}, 54.3{\%}, and 35.9{\%}, respectively, on day 1 of ranitidine administration and was 45.8{\%}, 30.1{\%}, and 20.8{\%} on day 5 (p < 0.005 for each comparison). Subjects' Helicobacter pylori status did not affect the antisecretory effect of ranitidine. There was no alteration in ranitidine pharmacokinetics to account for its reduced antisecretory effect. CONCLUSION: This study has demonstrated a statistically significant reduction in the antisecretory effect of ranitidine within 5 days of continuous administration which is not explained by altered ranitidine pharmacokinetics. This is further evidence for the development of a form of pharmacological tolerance to an H2-receptor antagonist within a few days of continuous daily dosing.",
author = "Leonard Lachman and Colin Howden",
year = "2000",
month = "1",
day = "1",
doi = "10.1016/S0002-9270(99)00760-1",
language = "English (US)",
volume = "95",
pages = "57--61",
journal = "American Journal of Gastroenterology",
issn = "0002-9270",
publisher = "Nature Publishing Group",
number = "1",

}

TY - JOUR

T1 - Twenty-four-hour intragastric pH

T2 - Tolerance within 5 days of continuous ranitidine administration

AU - Lachman, Leonard

AU - Howden, Colin

PY - 2000/1/1

Y1 - 2000/1/1

N2 - OBJECTIVE: To investigate further the phenomenon of pharmacological tolerance to H2-receptor antagonists, we undertook a study of the antisecretory effect of ranitidine with continuous daily administration. METHODS: A total of 28 healthy male volunteers were given ranitidine 150 mg q.i.d. for 5 days. Twenty-four-hour intragastric pH monitoring was performed predosing and on days 1 and 5 of ranitidine administration. Serial blood samples were collected on days 1 and 5 of ranitidine administration for pharmacokinetics. RESULTS: Mean 24-h intragastric pH was 2.62 predosing, 4.22 on day 1 of ranitidine administration and 3.28 on day 5 (p = 0.001, ranitidine day 1 vs day 5). Intragastric pH was >3, 4, and 5 for 69.9%, 54.3%, and 35.9%, respectively, on day 1 of ranitidine administration and was 45.8%, 30.1%, and 20.8% on day 5 (p < 0.005 for each comparison). Subjects' Helicobacter pylori status did not affect the antisecretory effect of ranitidine. There was no alteration in ranitidine pharmacokinetics to account for its reduced antisecretory effect. CONCLUSION: This study has demonstrated a statistically significant reduction in the antisecretory effect of ranitidine within 5 days of continuous administration which is not explained by altered ranitidine pharmacokinetics. This is further evidence for the development of a form of pharmacological tolerance to an H2-receptor antagonist within a few days of continuous daily dosing.

AB - OBJECTIVE: To investigate further the phenomenon of pharmacological tolerance to H2-receptor antagonists, we undertook a study of the antisecretory effect of ranitidine with continuous daily administration. METHODS: A total of 28 healthy male volunteers were given ranitidine 150 mg q.i.d. for 5 days. Twenty-four-hour intragastric pH monitoring was performed predosing and on days 1 and 5 of ranitidine administration. Serial blood samples were collected on days 1 and 5 of ranitidine administration for pharmacokinetics. RESULTS: Mean 24-h intragastric pH was 2.62 predosing, 4.22 on day 1 of ranitidine administration and 3.28 on day 5 (p = 0.001, ranitidine day 1 vs day 5). Intragastric pH was >3, 4, and 5 for 69.9%, 54.3%, and 35.9%, respectively, on day 1 of ranitidine administration and was 45.8%, 30.1%, and 20.8% on day 5 (p < 0.005 for each comparison). Subjects' Helicobacter pylori status did not affect the antisecretory effect of ranitidine. There was no alteration in ranitidine pharmacokinetics to account for its reduced antisecretory effect. CONCLUSION: This study has demonstrated a statistically significant reduction in the antisecretory effect of ranitidine within 5 days of continuous administration which is not explained by altered ranitidine pharmacokinetics. This is further evidence for the development of a form of pharmacological tolerance to an H2-receptor antagonist within a few days of continuous daily dosing.

UR - http://www.scopus.com/inward/record.url?scp=0033987730&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0033987730&partnerID=8YFLogxK

U2 - 10.1016/S0002-9270(99)00760-1

DO - 10.1016/S0002-9270(99)00760-1

M3 - Article

VL - 95

SP - 57

EP - 61

JO - American Journal of Gastroenterology

JF - American Journal of Gastroenterology

SN - 0002-9270

IS - 1

ER -