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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
2
|
| pubmed:dateCreated |
1998-3-20
|
| pubmed:abstractText |
The mutual inhibition between quinine and etoposide with their major metabolic pathways (i.e. quinine 3-hydroxylation and etoposide 3'-demethylation) was examined in vitro by human liver microsomes. Etoposide inhibited quinine 3-hydroxylation in a concentration-dependent manner with a mean IC50 of 65 microM. The mean maximum inhibition by etoposide (100 micro) of quinine 3-hydroxylation was about 60%. Similarly, etoposide 3'-demethylation was inhibited by quinine in a concentration-related manner with a mean IC50 value of 90 microM. The mean maximum inhibition by quinine (100 M) of etoposide 3'-demethylation was about 52%. An excellent correlation (r = 0.947, p < 0.01) between quinine 3-hydroxylase and etoposide 3'-demethylase activities in six different human liver microsomes was observed. Two inhibitors of CYP3A4, ketoconazole (1 microM) and troleandomycin (100 microM), inhibited quinine 3-hydroxylation by about 90% and 80%, and etoposide 3'-demethylation by about 75% and 65%, respectively. We conclude that quinine and etoposide mutually inhibit the metabolism of each other, consistent with the previous finding that CYP3A4 catalyzes the metabolism of both substrates.
|
| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
IM
|
| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/3-hydroxyquinidine,
http://linkedlifedata.com/resource/pubmed/chemical/CYP3A protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/CYP3A4 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Cytochrome P-450 CYP3A,
http://linkedlifedata.com/resource/pubmed/chemical/Cytochrome P-450 Enzyme System,
http://linkedlifedata.com/resource/pubmed/chemical/Etoposide,
http://linkedlifedata.com/resource/pubmed/chemical/Ketoconazole,
http://linkedlifedata.com/resource/pubmed/chemical/Mixed Function Oxygenases,
http://linkedlifedata.com/resource/pubmed/chemical/Oxidoreductases, O-Demethylating,
http://linkedlifedata.com/resource/pubmed/chemical/Quinidine,
http://linkedlifedata.com/resource/pubmed/chemical/Quinine,
http://linkedlifedata.com/resource/pubmed/chemical/Troleandomycin
|
| pubmed:status |
MEDLINE
|
| pubmed:month |
Feb
|
| pubmed:issn |
0090-9556
|
| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:volume |
26
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
188-91
|
| pubmed:dateRevised |
2008-11-21
|
| pubmed:meshHeading |
pubmed-meshheading:9456308-Cytochrome P-450 CYP3A,
pubmed-meshheading:9456308-Cytochrome P-450 Enzyme System,
pubmed-meshheading:9456308-Etoposide,
pubmed-meshheading:9456308-Humans,
pubmed-meshheading:9456308-Ketoconazole,
pubmed-meshheading:9456308-Microsomes, Liver,
pubmed-meshheading:9456308-Mixed Function Oxygenases,
pubmed-meshheading:9456308-Oxidoreductases, O-Demethylating,
pubmed-meshheading:9456308-Quinidine,
pubmed-meshheading:9456308-Quinine,
pubmed-meshheading:9456308-Troleandomycin
|
| pubmed:year |
1998
|
| pubmed:articleTitle |
Mutual inhibition between quinine and etoposide by human liver microsomes. Evidence for cytochrome P4503A4 involvement in their major metabolic pathways.
|
| pubmed:affiliation |
Department of Clinical Pharmacology, Research Institute, International Medical Center of Japan, Tokyo, Japan.
|
| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
|