Ontology type: schema:ScholarlyArticle
2007-05
AUTHORSN A Farid, C D Payne, D S Small, K J Winters, C S Ernest, J T Brandt, C Darstein, J A Jakubowski, D E Salazar
ABSTRACTPrasugrel and clopidogrel inhibit platelet aggregation through active metabolite formation. Prasugrel's active metabolite (R-138727) is formed primarily by cytochrome P450 (CYP) 3A and CYP2B6, with roles for CYP2C9 and CYP2C19. Clopidogrel's activation involves two sequential steps by CYP3A, CYP1A2, CYP2C9, CYP2C19, and/or CYP2B6. In a randomized crossover study, healthy subjects received a loading dose (LD) of prasugrel (60 mg) or clopidogrel (300 mg), followed by five daily maintenance doses (MDs) (15 and 75 mg, respectively) with or without the potent CYP3A inhibitor ketoconazole (400 mg/day). Subjects had a 2-week washout between periods. Ketoconazole decreased R-138727 and clopidogrel active metabolite Cmax (maximum plasma concentration) 34-61% after prasugrel and clopidogrel dosing. Ketoconazole did not affect R-138727 exposure or prasugrel's inhibition of platelet aggregation (IPA). Ketoconazole decreased clopidogrel's active metabolite AUC0-24 (area under the concentration-time curve to 24 h postdose) 22% (LD) to 29% (MD) and reduced IPA 28% (LD) to 33% (MD). We conclude that CYP3A4 and CYP3A5 inhibition by ketoconazole affects formation of clopidogrel's but not prasugrel's active metabolite. The decreased formation of clopidogrel's active metabolite is associated with reduced IPA. More... »
PAGES735-741
http://scigraph.springernature.com/pub.10.1038/sj.clpt.6100139
DOIhttp://dx.doi.org/10.1038/sj.clpt.6100139
DIMENSIONShttps://app.dimensions.ai/details/publication/pub.1006304268
PUBMEDhttps://www.ncbi.nlm.nih.gov/pubmed/17361128
JSON-LD is the canonical representation for SciGraph data.
TIP: You can open this SciGraph record using an external JSON-LD service: JSON-LD Playground Google SDTT
[
{
"@context": "https://springernature.github.io/scigraph/jsonld/sgcontext.json",
"about": [
{
"id": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/1115",
"inDefinedTermSet": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/",
"name": "Pharmacology and Pharmaceutical Sciences",
"type": "DefinedTerm"
},
{
"id": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/11",
"inDefinedTermSet": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/",
"name": "Medical and Health Sciences",
"type": "DefinedTerm"
},
{
"inDefinedTermSet": "https://www.nlm.nih.gov/mesh/",
"name": "Adult",
"type": "DefinedTerm"
},
{
"inDefinedTermSet": "https://www.nlm.nih.gov/mesh/",
"name": "Area Under Curve",
"type": "DefinedTerm"
},
{
"inDefinedTermSet": "https://www.nlm.nih.gov/mesh/",
"name": "Clopidogrel",
"type": "DefinedTerm"
},
{
"inDefinedTermSet": "https://www.nlm.nih.gov/mesh/",
"name": "Cross-Over Studies",
"type": "DefinedTerm"
},
{
"inDefinedTermSet": "https://www.nlm.nih.gov/mesh/",
"name": "Cytochrome P-450 CYP3A Inhibitors",
"type": "DefinedTerm"
},
{
"inDefinedTermSet": "https://www.nlm.nih.gov/mesh/",
"name": "Double-Blind Method",
"type": "DefinedTerm"
},
{
"inDefinedTermSet": "https://www.nlm.nih.gov/mesh/",
"name": "Drug Interactions",
"type": "DefinedTerm"
},
{
"inDefinedTermSet": "https://www.nlm.nih.gov/mesh/",
"name": "Enzyme Inhibitors",
"type": "DefinedTerm"
},
{
"inDefinedTermSet": "https://www.nlm.nih.gov/mesh/",
"name": "Female",
"type": "DefinedTerm"
},
{
"inDefinedTermSet": "https://www.nlm.nih.gov/mesh/",
"name": "Humans",
"type": "DefinedTerm"
},
{
"inDefinedTermSet": "https://www.nlm.nih.gov/mesh/",
"name": "Ketoconazole",
"type": "DefinedTerm"
},
{
"inDefinedTermSet": "https://www.nlm.nih.gov/mesh/",
"name": "Male",
"type": "DefinedTerm"
},
{
"inDefinedTermSet": "https://www.nlm.nih.gov/mesh/",
"name": "Middle Aged",
"type": "DefinedTerm"
},
{
"inDefinedTermSet": "https://www.nlm.nih.gov/mesh/",
"name": "Piperazines",
"type": "DefinedTerm"
},
{
"inDefinedTermSet": "https://www.nlm.nih.gov/mesh/",
"name": "Platelet Aggregation",
"type": "DefinedTerm"
},
{
"inDefinedTermSet": "https://www.nlm.nih.gov/mesh/",
"name": "Platelet Aggregation Inhibitors",
"type": "DefinedTerm"
},
{
"inDefinedTermSet": "https://www.nlm.nih.gov/mesh/",
"name": "Prasugrel Hydrochloride",
"type": "DefinedTerm"
},
{
"inDefinedTermSet": "https://www.nlm.nih.gov/mesh/",
"name": "Thiophenes",
"type": "DefinedTerm"
},
{
"inDefinedTermSet": "https://www.nlm.nih.gov/mesh/",
"name": "Ticlopidine",
"type": "DefinedTerm"
}
],
"author": [
{
"affiliation": {
"alternateName": "Eli Lilly (United States)",
"id": "https://www.grid.ac/institutes/grid.417540.3",
"name": [
"Lilly Research Laboratories, Eli Lilly and Company Indianapolis Indiana USA"
],
"type": "Organization"
},
"familyName": "Farid",
"givenName": "N A",
"id": "sg:person.01255414044.69",
"sameAs": [
"https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01255414044.69"
],
"type": "Person"
},
{
"affiliation": {
"name": [
"Lilly Research Center Ltd Windlesham UK"
],
"type": "Organization"
},
"familyName": "Payne",
"givenName": "C D",
"id": "sg:person.01224546355.86",
"sameAs": [
"https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01224546355.86"
],
"type": "Person"
},
{
"affiliation": {
"alternateName": "Eli Lilly (United States)",
"id": "https://www.grid.ac/institutes/grid.417540.3",
"name": [
"Lilly Research Laboratories, Eli Lilly and Company Indianapolis Indiana USA"
],
"type": "Organization"
},
"familyName": "Small",
"givenName": "D S",
"id": "sg:person.01126325126.28",
"sameAs": [
"https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01126325126.28"
],
"type": "Person"
},
{
"affiliation": {
"alternateName": "Eli Lilly (United States)",
"id": "https://www.grid.ac/institutes/grid.417540.3",
"name": [
"Lilly Research Laboratories, Eli Lilly and Company Indianapolis Indiana USA"
],
"type": "Organization"
},
"familyName": "Winters",
"givenName": "K J",
"id": "sg:person.01046045655.15",
"sameAs": [
"https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01046045655.15"
],
"type": "Person"
},
{
"affiliation": {
"alternateName": "Eli Lilly (United States)",
"id": "https://www.grid.ac/institutes/grid.417540.3",
"name": [
"Lilly Research Laboratories, Eli Lilly and Company Indianapolis Indiana USA"
],
"type": "Organization"
},
"familyName": "Ernest",
"givenName": "C S",
"id": "sg:person.01252000221.39",
"sameAs": [
"https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01252000221.39"
],
"type": "Person"
},
{
"affiliation": {
"alternateName": "Eli Lilly (United States)",
"id": "https://www.grid.ac/institutes/grid.417540.3",
"name": [
"Lilly Research Laboratories, Eli Lilly and Company Indianapolis Indiana USA"
],
"type": "Organization"
},
"familyName": "Brandt",
"givenName": "J T",
"id": "sg:person.01340774755.46",
"sameAs": [
"https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01340774755.46"
],
"type": "Person"
},
{
"affiliation": {
"alternateName": "Eli Lilly (United States)",
"id": "https://www.grid.ac/institutes/grid.417540.3",
"name": [
"Lilly Research Laboratories, Eli Lilly and Company Indianapolis Indiana USA"
],
"type": "Organization"
},
"familyName": "Darstein",
"givenName": "C",
"id": "sg:person.01137756171.46",
"sameAs": [
"https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01137756171.46"
],
"type": "Person"
},
{
"affiliation": {
"alternateName": "Eli Lilly (United States)",
"id": "https://www.grid.ac/institutes/grid.417540.3",
"name": [
"Lilly Research Laboratories, Eli Lilly and Company Indianapolis Indiana USA"
],
"type": "Organization"
},
"familyName": "Jakubowski",
"givenName": "J A",
"id": "sg:person.0756623644.24",
"sameAs": [
"https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0756623644.24"
],
"type": "Person"
},
{
"affiliation": {
"alternateName": "Daiichi Sankyo (United States)",
"id": "https://www.grid.ac/institutes/grid.428496.5",
"name": [
"Daiichi Sankyo Inc. Parsippany New Jersey USA"
],
"type": "Organization"
},
"familyName": "Salazar",
"givenName": "D E",
"id": "sg:person.014714657504.26",
"sameAs": [
"https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.014714657504.26"
],
"type": "Person"
}
],
"citation": [
{
"id": "https://doi.org/10.1161/01.cir.0000047060.60595.cc",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1010854770"
],
"type": "CreativeWork"
},
{
"id": "https://doi.org/10.1182/blood-2002-10-3027",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1014797573"
],
"type": "CreativeWork"
},
{
"id": "https://doi.org/10.1503/cmaj.060664",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1016886879"
],
"type": "CreativeWork"
},
{
"id": "https://doi.org/10.1503/cmaj.060664",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1016886879"
],
"type": "CreativeWork"
},
{
"id": "https://doi.org/10.1111/j.1365-2141.1985.tb07467.x",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1030449319"
],
"type": "CreativeWork"
},
{
"id": "https://doi.org/10.1093/eurheartj/ehi877",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1033526755"
],
"type": "CreativeWork"
},
{
"id": "https://doi.org/10.1124/dmd.31.7.815",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1034066953"
],
"type": "CreativeWork"
},
{
"id": "https://doi.org/10.1182/blood-2006-04-013052",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1034582023"
],
"type": "CreativeWork"
},
{
"id": "https://doi.org/10.1161/01.cir.0000112378.09325.f9",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1037144438"
],
"type": "CreativeWork"
},
{
"id": "https://doi.org/10.1124/dmd.105.007989",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1038051799"
],
"type": "CreativeWork"
},
{
"id": "https://doi.org/10.1124/dmd.31.1.53",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1040947861"
],
"type": "CreativeWork"
},
{
"id": "https://doi.org/10.1038/sj.bjp.0703237",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1041733321"
],
"type": "CreativeWork"
},
{
"id": "https://doi.org/10.1056/nejmoa010746",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1042739677"
],
"type": "CreativeWork"
},
{
"id": "https://doi.org/10.1016/j.amjcard.2006.09.078",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1050252358"
],
"type": "CreativeWork"
},
{
"id": "https://doi.org/10.1161/01.cir.0000099507.32936.c0",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1051697653"
],
"type": "CreativeWork"
},
{
"id": "https://doi.org/10.1111/j.1742-7843.2005.pto960203.x",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1052432532"
],
"type": "CreativeWork"
},
{
"id": "https://doi.org/10.1002/rcm.2813",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1052975930"
],
"type": "CreativeWork"
},
{
"id": "https://doi.org/10.1016/j.ahj.2006.10.010",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1053653581"
],
"type": "CreativeWork"
},
{
"id": "https://doi.org/10.1016/s0195-668x(03)00442-1",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1054625464"
],
"type": "CreativeWork"
},
{
"id": "https://doi.org/10.1055/s-0037-1614133",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1074741659"
],
"type": "CreativeWork"
},
{
"id": "https://doi.org/10.1055/s-0037-1613462",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1075277395"
],
"type": "CreativeWork"
}
],
"datePublished": "2007-05",
"datePublishedReg": "2007-05-01",
"description": "Prasugrel and clopidogrel inhibit platelet aggregation through active metabolite formation. Prasugrel's active metabolite (R-138727) is formed primarily by cytochrome P450 (CYP) 3A and CYP2B6, with roles for CYP2C9 and CYP2C19. Clopidogrel's activation involves two sequential steps by CYP3A, CYP1A2, CYP2C9, CYP2C19, and/or CYP2B6. In a randomized crossover study, healthy subjects received a loading dose (LD) of prasugrel (60 mg) or clopidogrel (300 mg), followed by five daily maintenance doses (MDs) (15 and 75 mg, respectively) with or without the potent CYP3A inhibitor ketoconazole (400 mg/day). Subjects had a 2-week washout between periods. Ketoconazole decreased R-138727 and clopidogrel active metabolite Cmax (maximum plasma concentration) 34-61% after prasugrel and clopidogrel dosing. Ketoconazole did not affect R-138727 exposure or prasugrel's inhibition of platelet aggregation (IPA). Ketoconazole decreased clopidogrel's active metabolite AUC0-24 (area under the concentration-time curve to 24 h postdose) 22% (LD) to 29% (MD) and reduced IPA 28% (LD) to 33% (MD). We conclude that CYP3A4 and CYP3A5 inhibition by ketoconazole affects formation of clopidogrel's but not prasugrel's active metabolite. The decreased formation of clopidogrel's active metabolite is associated with reduced IPA.",
"genre": "research_article",
"id": "sg:pub.10.1038/sj.clpt.6100139",
"inLanguage": [
"en"
],
"isAccessibleForFree": false,
"isPartOf": [
{
"id": "sg:journal.1017409",
"issn": [
"0009-9236",
"1532-6535"
],
"name": "Clinical Pharmacology & Therapeutics",
"type": "Periodical"
},
{
"issueNumber": "5",
"type": "PublicationIssue"
},
{
"type": "PublicationVolume",
"volumeNumber": "81"
}
],
"name": "Cytochrome P450 3A Inhibition by Ketoconazole Affects Prasugrel and Clopidogrel Pharmacokinetics and Pharmacodynamics Differently",
"pagination": "735-741",
"productId": [
{
"name": "readcube_id",
"type": "PropertyValue",
"value": [
"1e078ce93f9c4d8e2c19caf286e610f45deca7bc76978a12918b6e7371d5e00a"
]
},
{
"name": "pubmed_id",
"type": "PropertyValue",
"value": [
"17361128"
]
},
{
"name": "nlm_unique_id",
"type": "PropertyValue",
"value": [
"0372741"
]
},
{
"name": "doi",
"type": "PropertyValue",
"value": [
"10.1038/sj.clpt.6100139"
]
},
{
"name": "dimensions_id",
"type": "PropertyValue",
"value": [
"pub.1006304268"
]
}
],
"sameAs": [
"https://doi.org/10.1038/sj.clpt.6100139",
"https://app.dimensions.ai/details/publication/pub.1006304268"
],
"sdDataset": "articles",
"sdDatePublished": "2019-04-11T13:00",
"sdLicense": "https://scigraph.springernature.com/explorer/license/",
"sdPublisher": {
"name": "Springer Nature - SN SciGraph project",
"type": "Organization"
},
"sdSource": "s3://com-uberresearch-data-dimensions-target-20181106-alternative/cleanup/v134/2549eaecd7973599484d7c17b260dba0a4ecb94b/merge/v9/a6c9fde33151104705d4d7ff012ea9563521a3ce/jats-lookup/v90/0000000365_0000000365/records_71704_00000000.jsonl",
"type": "ScholarlyArticle",
"url": "http://onlinelibrary.wiley.com/doi/10.1038/sj.clpt.6100139/abstract"
}
]
Download the RDF metadata as: json-ld nt turtle xml License info
JSON-LD is a popular format for linked data which is fully compatible with JSON.
curl -H 'Accept: application/ld+json' 'https://scigraph.springernature.com/pub.10.1038/sj.clpt.6100139'
N-Triples is a line-based linked data format ideal for batch operations.
curl -H 'Accept: application/n-triples' 'https://scigraph.springernature.com/pub.10.1038/sj.clpt.6100139'
Turtle is a human-readable linked data format.
curl -H 'Accept: text/turtle' 'https://scigraph.springernature.com/pub.10.1038/sj.clpt.6100139'
RDF/XML is a standard XML format for linked data.
curl -H 'Accept: application/rdf+xml' 'https://scigraph.springernature.com/pub.10.1038/sj.clpt.6100139'
This table displays all metadata directly associated to this object as RDF triples.
266 TRIPLES
21 PREDICATES
68 URIs
40 LITERALS
28 BLANK NODES