9616194

Source:http://linkedlifedata.com/resource/pubmed/id/9616194

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Predicate	Object
rdf:type	pubmed:Citation
lifeskim:mentions	umls-concept:C0040805, umls-concept:C0044170, umls-concept:C0086418, umls-concept:C0449416, umls-concept:C1176140, umls-concept:C1524026
pubmed:issue	6
pubmed:dateCreated	1998-7-1
pubmed:abstractText	The metabolism of the antidepressant drug trazodone to its active metabolite, m-chlorophenylpiperazine (mCPP), was studied in vitro using human liver microsomal preparations and cDNA-expressed human cytochrome P450 (P450) enzymes. The kinetics of mCPP formation from trazodone were determined, and three in vitro experiments were performed to identify the major P450 enzyme involved. Trazodone (100 microM) was incubated with 16 different human liver microsomal preparations characterized for activities of 7 different P450 isoforms. The production of mCPP correlated significantly with activity of cytochrome P4503A4 (CYP3A4) only. Trazodone (100 microM) was then incubated with microsomes from cells expressing human CYP1A1, CYP1A2, CYP2C8, CYP2C9arg, CYP2C9cys, CYP2C19, CYP2D6, or CYP3A4. Only incubations with CYP3A4 resulted in mCPP formation. In the third experiment, the CYP3A4 inhibitor ketoconazole was found to inhibit mCPP formation concentration dependently in both human liver microsomes and in microsomes from cells expressing human CYP3A4. The present results indicate that trazodone is a substrate for CYP3A4, that CYP3A4 is a major isoform involved in the production of mCPP from trazodone, and that there is the possibility of drug-drug interactions with trazodone and other substrates, inducers and/or inhibitors of CYP3A4.
pubmed:language	eng
pubmed:journal	http://linkedlifedata.com/resource/pubmed/journal/9421550
pubmed:citationSubset	IM
pubmed:chemical	http://linkedlifedata.com/resource/pubmed/chemical/1-(3-chlorophenyl)piperazine, http://linkedlifedata.com/resource/pubmed/chemical/Antidepressive Agents..., 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/Ketoconazole, http://linkedlifedata.com/resource/pubmed/chemical/Mixed Function Oxygenases, http://linkedlifedata.com/resource/pubmed/chemical/Piperazines, http://linkedlifedata.com/resource/pubmed/chemical/Serotonin Receptor Agonists, http://linkedlifedata.com/resource/pubmed/chemical/Trazodone
pubmed:status	MEDLINE
pubmed:month	Jun
pubmed:issn	0090-9556
pubmed:author	pubmed-author:BakerG BGB, pubmed-author:FangJJ, pubmed-author:RotzingerSS
pubmed:issnType	Print
pubmed:volume	26
pubmed:owner	NLM
pubmed:authorsComplete	Y
pubmed:pagination	572-5
pubmed:dateRevised	2010-11-18
pubmed:meshHeading	pubmed-meshheading:9616194-Antidepressive Agents, Second-Generation, pubmed-meshheading:9616194-Cytochrome P-450 CYP3A, pubmed-meshheading:9616194-Cytochrome P-450 Enzyme System, pubmed-meshheading:9616194-Humans, pubmed-meshheading:9616194-Ketoconazole, pubmed-meshheading:9616194-Microsomes, Liver, pubmed-meshheading:9616194-Mixed Function Oxygenases, pubmed-meshheading:9616194-Piperazines, pubmed-meshheading:9616194-Serotonin Receptor Agonists, pubmed-meshheading:9616194-Trazodone
pubmed:year	1998
pubmed:articleTitle	Trazodone is metabolized to m-chlorophenylpiperazine by CYP3A4 from human sources.
pubmed:affiliation	Neurochemical Research Unit, Department of Psychiatry, Mackenzie Health Sciences Center, University of Alberta, Edmonton, AB, T6G, 2B7, Canada.
pubmed:publicationType	Journal Article, Research Support, Non-U.S. Gov't