Linked Life Data

2892251

Source:http://linkedlifedata.com/resource/pubmed/id/2892251

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:dateCreated
1988-2-3
pubmed:abstractText
H2-receptor antagonists are among the most widely-used drugs in the world and, since many patients receive a variety of other drugs concomitantly, it is important to investigate the interaction potential of new H2-receptor antagonists such as nizatidine. It is well documented that cimetidine can inhibit the hepatic elimination of many drugs by binding to the cytochrome P-450 system. Therefore we investigated in vitro and in vivo the effects of nizatidine on drug metabolism. With rat liver microsomes the effects of nizatidine and four other H2-blockers (cimetidine, oxmetidine, ranitidine, famotidine) on the activity of three marker enzymes (aryl-hydrocarbon-hydroxylase, 7-ethoxycoumarin-O-deethylase, 7-ethoxy-resorufin-O-deethylase) were tested. While cimetidine and oxmetidine exhibited marked and dose-dependent inhibition of all three metabolic reactions, nizatidine showed some weak inhibition only at very high concentrations. Similarly, binding to cytochrome P-450 of human liver microsomes could be seen only with cimetidine and oxmetidine, whereas nizatidine did not affect the binding spectra. In nine healthy mal volunteers the pharmacokinetics of diazepam (10 mg po) was studied under the influence of nizatidine (300 mg day nocte). Nizatidine had no significant effect on the hepatic elimination of diazepam, as characterized by its elimination half-life (mean +/- SD) of 35.3 +/- 24.2 h (control) and 37.3 +/- 18.3 h (+ nizatidine) or its total plasma clearance of 28.2 +/-12.0 ml/min (control) and 26.7 +/- 10.4 ml/min (+ nizatidine). The formation of the major metabolite-desmethyldiazepam-was also unaffected by nizatidine.(ABSTRACT TRUNCATED AT 250 WORDS)
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
0085-5928
pubmed:author
pubmed:issnType
Print
pubmed:volume
136
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
18-23
pubmed:dateRevised
2008-2-13
pubmed:meshHeading
pubmed:year
1987
pubmed:articleTitle
Lack of effect of nizatidine on drug metabolism.
pubmed:affiliation
Dr. Margarete Fischer-Bosch-Institut für Klinische Pharmakologie, Stuttgart, FRG.
pubmed:publicationType
Journal Article, In Vitro