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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
3
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pubmed:dateCreated |
1994-9-28
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pubmed:abstractText |
All trans-retinoic acid (tr-RA) has been used to induce leukemic cell differentiation in patients with acute promyelocytic leukemia (APL). However, the duration of remission is brief and is associated with a progressive decrease in peak plasma concentrations following chronic dosing. 9-Cis-retinoic acid (9-cis-RA) has the potential to elicit the same effects as tr-RA, because it can bind and activate the same family of nuclear receptors. It is not known whether the pharmacokinetics of this novel compound resemble those of tr-RA. In this study, we report major differences in the uptake and pharmacokinetics between orally administered tr-RA and 9-cis-RA in the plasma of nude mice. Following a single initial oral administration of either isomer, the plasma peak time of 9-cis-RA (15-30 min) occurred earlier than that of tr-RA (60-180 min), but with lower plasma concentrations and area under the concentration-time curve (AUC) value. A decrease in the AUC of plasma tr-RA was seen in animals that were given a second dose 2 days after the first dose. In contrast, an increase in the AUC of plasma 9-cis-RA was seen in animals that were given a second dose 2 days after the first dose. This increase was due to the appearance of a second 9-cis-RA peak at 180 min. When liarozole, an inhibitor of tr-RA metabolism, was coadministered with the initial tr-RA dose or a second tr-RA dose 2 weeks later, the AUC of plasma tr-RA was increased relative to tr-RA alone.(ABSTRACT TRUNCATED AT 250 WORDS)
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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Imidazoles,
http://linkedlifedata.com/resource/pubmed/chemical/Retinoids,
http://linkedlifedata.com/resource/pubmed/chemical/Tretinoin,
http://linkedlifedata.com/resource/pubmed/chemical/Vitamin A,
http://linkedlifedata.com/resource/pubmed/chemical/liarozole
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pubmed:status |
MEDLINE
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pubmed:issn |
0090-9556
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
22
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
451-8
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pubmed:dateRevised |
2007-11-14
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pubmed:meshHeading |
pubmed-meshheading:8070324-Administration, Oral,
pubmed-meshheading:8070324-Animals,
pubmed-meshheading:8070324-Chromatography, High Pressure Liquid,
pubmed-meshheading:8070324-Drug Interactions,
pubmed-meshheading:8070324-Imidazoles,
pubmed-meshheading:8070324-Isomerism,
pubmed-meshheading:8070324-Male,
pubmed-meshheading:8070324-Mice,
pubmed-meshheading:8070324-Mice, Inbred BALB C,
pubmed-meshheading:8070324-Mice, Nude,
pubmed-meshheading:8070324-Models, Biological,
pubmed-meshheading:8070324-Retinoids,
pubmed-meshheading:8070324-Tretinoin,
pubmed-meshheading:8070324-Vitamin A
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pubmed:articleTitle |
Differences in the pharmacokinetic properties of orally administered all-trans-retinoic acid and 9-cis-retinoic acid in the plasma of nude mice.
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pubmed:affiliation |
Department of Pharmacology, Cornell University Medical College, New York, NY 10021.
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pubmed:publicationType |
Journal Article,
Comparative Study,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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