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Interaction of rocuronium with human liver cytochromes P450
E. Anzenbacherova, A. Spicakova, L. Jourova, J. Ulrichova, M. Adamus, P. Bachleda, P. Anzenbacher,
Language English Country Japan
Document type Journal Article, Research Support, Non-U.S. Gov't
Grant support
NT13591
MZ0
CEP Register
Digital library NLK
Full text - Article
Source
NLK
Directory of Open Access Journals
from 2015
Free Medical Journals
from 2003
Open Access Digital Library
from 2015-01-01
ROAD: Directory of Open Access Scholarly Resources
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- MeSH
- Androstanols metabolism pharmacology MeSH
- Cytochrome P-450 CYP3A metabolism physiology MeSH
- Cytochrome P-450 CYP2C19 metabolism physiology MeSH
- Cytochrome P-450 CYP2C9 metabolism MeSH
- Cytochromes metabolism MeSH
- Diazepam pharmacology MeSH
- Hepatocytes metabolism MeSH
- Cytochrome P-450 Enzyme Inhibitors MeSH
- Microsomes, Liver enzymology MeSH
- Cells, Cultured MeSH
- Drug Interactions MeSH
- Humans MeSH
- Neuromuscular Nondepolarizing Agents pharmacology MeSH
- Cytochrome P-450 Enzyme System metabolism MeSH
- Binding Sites MeSH
- Dose-Response Relationship, Drug MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
Rocuronium is a neuromuscular blocking agent acting as a competitive antagonist of acetylcholine. Results of an inhibition of eight individual liver microsomal cytochromes P450 (CYP) are presented. As the patients are routinely premedicated with diazepam, possible interaction of diazepam with rocuronium has been also studied. Results indicated that rocuronium interacts with human liver microsomal CYPs by binding to the substrate site. Next, concentration dependent inhibition of liver microsomal CYP3A4 down to 42% (at rocuronium concentration 189 μM) was found. This effect has been confirmed with two CYP3A4 substrates, testosterone (formation of 6β-hydroxytestosterone) and diazepam (temazepam formation). CYP2C9 and CYP2C19 activities were inhibited down to 75-80% (at the same rocuronium concentration). Activities of other microsomal CYPs have not been inhibited by rocuronium. To prove the possibility of rocuronium interaction with other drugs (diazepam), the effect of rocuronium on formation of main diazepam metabolites, temazepam (by CYP3A4) and desmethyldiazepam, (also known as nordiazepam; formed by CYP2C19) in primary culture of human hepatocytes has been examined. Rocuronium has caused inhibition of both reactions by 20 and 15%, respectively. The results open a possibility that interactions of rocuronium with drugs metabolized by CYP3A4 (and possibly also CYP2C19) may be observed.
References provided by Crossref.org
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- $a Rocuronium is a neuromuscular blocking agent acting as a competitive antagonist of acetylcholine. Results of an inhibition of eight individual liver microsomal cytochromes P450 (CYP) are presented. As the patients are routinely premedicated with diazepam, possible interaction of diazepam with rocuronium has been also studied. Results indicated that rocuronium interacts with human liver microsomal CYPs by binding to the substrate site. Next, concentration dependent inhibition of liver microsomal CYP3A4 down to 42% (at rocuronium concentration 189 μM) was found. This effect has been confirmed with two CYP3A4 substrates, testosterone (formation of 6β-hydroxytestosterone) and diazepam (temazepam formation). CYP2C9 and CYP2C19 activities were inhibited down to 75-80% (at the same rocuronium concentration). Activities of other microsomal CYPs have not been inhibited by rocuronium. To prove the possibility of rocuronium interaction with other drugs (diazepam), the effect of rocuronium on formation of main diazepam metabolites, temazepam (by CYP3A4) and desmethyldiazepam, (also known as nordiazepam; formed by CYP2C19) in primary culture of human hepatocytes has been examined. Rocuronium has caused inhibition of both reactions by 20 and 15%, respectively. The results open a possibility that interactions of rocuronium with drugs metabolized by CYP3A4 (and possibly also CYP2C19) may be observed.
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