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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
2
|
| pubmed:dateCreated |
1997-7-8
|
| pubmed:abstractText |
Pharmacokinetics of metyrapone and metyrapol enantiomers was studied in the rat to determine the stereoselective reductive metabolism of metyrapone. The HPLC method using a chiral column was developed for the stereoselective analysis of metyrapol enantiomers in rat plasma. The AUC ratio of (-)- and (+)-metyrapol appeared in rat plasma after i.v. administration of metyrapone was about 3:1. The interconversion of (-)- or (+)-metyrapol to its antipode was negligible, and the reverse reaction from metyrapol to metyrapone was insignificant. There were similar kinetic parameters of (-)-metyrapol to those of (+)-metyrapol after i.v. administration of racemic metyrapol. These results indicate metyrapone displays product-stereoselective reductive metabolism in the rat. The inhibition of steroid 11 beta-hydroxylase by metyrapone, racemic metyrapol, (-)-metyrapol or (+)-metyrapol was analyzed in rat adrenal homogenates. Metyrapol was equally as potent as metyrapone in the inhibition of steroid 11 beta-hydroxylase and each enantiomer of metyrapol showed similar inhibitory activity on the rat adrenal steroid 11 beta-hydroxylase. These results indicate there is an insignificant difference in the inhibitory effects on steroid 11 beta-hydroxylase of metyrapol enantiomers, and that the inhibitory effects of metyrapol may be involved in the pharmacological activity of metyrapone in vivo.
|
| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
IM
|
| pubmed:chemical | |
| pubmed:status |
MEDLINE
|
| pubmed:month |
Feb
|
| pubmed:issn |
0918-6158
|
| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:volume |
20
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
188-92
|
| pubmed:dateRevised |
2003-11-14
|
| pubmed:meshHeading |
pubmed-meshheading:9057984-Adrenal Glands,
pubmed-meshheading:9057984-Animals,
pubmed-meshheading:9057984-Enzyme Inhibitors,
pubmed-meshheading:9057984-Male,
pubmed-meshheading:9057984-Metyrapone,
pubmed-meshheading:9057984-Rats,
pubmed-meshheading:9057984-Rats, Wistar,
pubmed-meshheading:9057984-Stereoisomerism,
pubmed-meshheading:9057984-Steroid 11-beta-Hydroxylase
|
| pubmed:year |
1997
|
| pubmed:articleTitle |
Stereoselective reductive metabolism of metyrapone and inhibitory activity of metyrapone metabolites, metyrapol enantiomers, on steroid 11 beta-hydroxylase in the rat.
|
| pubmed:affiliation |
Department of Pharmaceutics, Kobe Pharmaceutical University, Japan.
|
| pubmed:publicationType |
Journal Article
|