Inhibition of microsomal drug metabolism by histamine H2-receptor antagonists studied in vivo and in vitro in rodents

Kermit V Speeg, R. V. Patwardhan, G. R. Avant, M. G. Mitchell, S. Schenker

Research output: Contribution to journalArticle

112 Citations (Scopus)

Abstract

Cimetidine has been demonstrated to impair microsomal oxidative drug metabolism in a dose-dependent manner in an animal model. The inhibition has also been shown to be rapid, occurring after a single dose. In the present study we demonstrate that recovery from inhibition after cimetidine withdrawal is also rapid, occurring within 24 h. Furthermore, chronic dosing with cimetidine does not result in tolerance to the inhibitory effect. Other H2-antihistamines have also been studied both in vivo and in vitro. Based on spectral binding changes, in vitro enzyme assays and in vivo aminopyrine breath tests, ICI 125,211, ranitidine, and cimetidine sulfoxide are much less inhibitory than cimetidine. The ability of cimetidine to impair the elimination of aminopyrine in the mouse after acute liver damage was greater than in the normal mouse.

Original languageEnglish (US)
Pages (from-to)89-96
Number of pages8
JournalGastroenterology
Volume82
Issue number1
StatePublished - 1982
Externally publishedYes

Fingerprint

Histamine H2 Antagonists
Cimetidine
Rodentia
Aminopyrine
Pharmaceutical Preparations
Breath Tests
Ranitidine
Histamine Antagonists
Enzyme Assays
Animal Models
In Vitro Techniques
Liver

ASJC Scopus subject areas

  • Gastroenterology

Cite this

Inhibition of microsomal drug metabolism by histamine H2-receptor antagonists studied in vivo and in vitro in rodents. / Speeg, Kermit V; Patwardhan, R. V.; Avant, G. R.; Mitchell, M. G.; Schenker, S.

In: Gastroenterology, Vol. 82, No. 1, 1982, p. 89-96.

Research output: Contribution to journalArticle

Speeg, Kermit V ; Patwardhan, R. V. ; Avant, G. R. ; Mitchell, M. G. ; Schenker, S. / Inhibition of microsomal drug metabolism by histamine H2-receptor antagonists studied in vivo and in vitro in rodents. In: Gastroenterology. 1982 ; Vol. 82, No. 1. pp. 89-96.
@article{3ab47edd4b5748e08c9a8daef9b102d5,
title = "Inhibition of microsomal drug metabolism by histamine H2-receptor antagonists studied in vivo and in vitro in rodents",
abstract = "Cimetidine has been demonstrated to impair microsomal oxidative drug metabolism in a dose-dependent manner in an animal model. The inhibition has also been shown to be rapid, occurring after a single dose. In the present study we demonstrate that recovery from inhibition after cimetidine withdrawal is also rapid, occurring within 24 h. Furthermore, chronic dosing with cimetidine does not result in tolerance to the inhibitory effect. Other H2-antihistamines have also been studied both in vivo and in vitro. Based on spectral binding changes, in vitro enzyme assays and in vivo aminopyrine breath tests, ICI 125,211, ranitidine, and cimetidine sulfoxide are much less inhibitory than cimetidine. The ability of cimetidine to impair the elimination of aminopyrine in the mouse after acute liver damage was greater than in the normal mouse.",
author = "Speeg, {Kermit V} and Patwardhan, {R. V.} and Avant, {G. R.} and Mitchell, {M. G.} and S. Schenker",
year = "1982",
language = "English (US)",
volume = "82",
pages = "89--96",
journal = "Gastroenterology",
issn = "0016-5085",
publisher = "W.B. Saunders Ltd",
number = "1",

}

TY - JOUR

T1 - Inhibition of microsomal drug metabolism by histamine H2-receptor antagonists studied in vivo and in vitro in rodents

AU - Speeg, Kermit V

AU - Patwardhan, R. V.

AU - Avant, G. R.

AU - Mitchell, M. G.

AU - Schenker, S.

PY - 1982

Y1 - 1982

N2 - Cimetidine has been demonstrated to impair microsomal oxidative drug metabolism in a dose-dependent manner in an animal model. The inhibition has also been shown to be rapid, occurring after a single dose. In the present study we demonstrate that recovery from inhibition after cimetidine withdrawal is also rapid, occurring within 24 h. Furthermore, chronic dosing with cimetidine does not result in tolerance to the inhibitory effect. Other H2-antihistamines have also been studied both in vivo and in vitro. Based on spectral binding changes, in vitro enzyme assays and in vivo aminopyrine breath tests, ICI 125,211, ranitidine, and cimetidine sulfoxide are much less inhibitory than cimetidine. The ability of cimetidine to impair the elimination of aminopyrine in the mouse after acute liver damage was greater than in the normal mouse.

AB - Cimetidine has been demonstrated to impair microsomal oxidative drug metabolism in a dose-dependent manner in an animal model. The inhibition has also been shown to be rapid, occurring after a single dose. In the present study we demonstrate that recovery from inhibition after cimetidine withdrawal is also rapid, occurring within 24 h. Furthermore, chronic dosing with cimetidine does not result in tolerance to the inhibitory effect. Other H2-antihistamines have also been studied both in vivo and in vitro. Based on spectral binding changes, in vitro enzyme assays and in vivo aminopyrine breath tests, ICI 125,211, ranitidine, and cimetidine sulfoxide are much less inhibitory than cimetidine. The ability of cimetidine to impair the elimination of aminopyrine in the mouse after acute liver damage was greater than in the normal mouse.

UR - http://www.scopus.com/inward/record.url?scp=0020077209&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0020077209&partnerID=8YFLogxK

M3 - Article

C2 - 6118315

AN - SCOPUS:0020077209

VL - 82

SP - 89

EP - 96

JO - Gastroenterology

JF - Gastroenterology

SN - 0016-5085

IS - 1

ER -