Effects of Ketoconazole, a CYP4F2 Inhibitor, and CYP4F2*3 Genetic Polymorphism on Pharmacokinetics of Vitamin K-1
DC Field | Value | Language |
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dc.contributor.author | Park, Jin-Woo | - |
dc.contributor.author | Kim, Kyoung-Ah | - |
dc.contributor.author | Park, Ji-Young | - |
dc.date.accessioned | 2021-09-01T01:28:25Z | - |
dc.date.available | 2021-09-01T01:28:25Z | - |
dc.date.created | 2021-06-18 | - |
dc.date.issued | 2019-11 | - |
dc.identifier.issn | 0091-2700 | - |
dc.identifier.uri | https://scholar.korea.ac.kr/handle/2021.sw.korea/62109 | - |
dc.description.abstract | The objective of this study was to evaluate whether cytochrome P450 (CYP)4F2 is involved in the exposure of vitamin K-1 through a drug interaction study with ketoconazole, a CYP4F2 inhibitor, and a pharmacogenetic study with CYP4F2*3. Twenty-one participants with different CYP4F2*3 polymorphisms were enrolled (8 for *1/*1, 7 for *1/*3, and 6 for *3/*3). All participants were treated twice daily for 5 days with 200 mg of ketoconazole or placebo. Finally, a single dose of 10 mg vitamin K-1 was administered, plasma levels of vitamin K-1 were measured, and its pharmacokinetics was assessed. Ketoconazole elevated the plasma levels of vitamin K-1 and increased the average area under the concentration-time curve (AUC(inf)) and peak concentration by 41% and 40%, respectively. CYP4F2*3 polymorphism also affected plasma levels of vitamin K-1 and its pharmacokinetics in a gene dose-dependent manner. The average AUC(inf) value was 659.8 ng center dot h/mL for CYP4F2*1/*1, 878.1 ng center dot h/mL for CYP4F2*1/*3, and 1125.2 ng center dot h/mL for CYP4F2*3/*3 (P = .010). This study revealed that ketoconazole and CYP4F2*3 polymorphism substantially increased the exposure of vitamin K-1 in humans. These findings provide a plausible explanation for variations in warfarin dose requirements resulting from interindividual variations in vitamin K-1 exposure due to CYP4F2-related drug interactions and genetic polymorphisms. | - |
dc.language | English | - |
dc.language.iso | en | - |
dc.publisher | WILEY | - |
dc.subject | OMEGA-HYDROXYLATION | - |
dc.subject | CHINESE PATIENTS | - |
dc.subject | ISCHEMIC-STROKE | - |
dc.subject | HUMAN LIVER | - |
dc.subject | WARFARIN | - |
dc.subject | VKORC1 | - |
dc.subject | 20-HETE | - |
dc.subject | ENZYMES | - |
dc.subject | METABOLISM | - |
dc.subject | VARIANT | - |
dc.title | Effects of Ketoconazole, a CYP4F2 Inhibitor, and CYP4F2*3 Genetic Polymorphism on Pharmacokinetics of Vitamin K-1 | - |
dc.type | Article | - |
dc.contributor.affiliatedAuthor | Park, Ji-Young | - |
dc.identifier.doi | 10.1002/jcph.1444 | - |
dc.identifier.scopusid | 2-s2.0-85072747337 | - |
dc.identifier.wosid | 000488637700003 | - |
dc.identifier.bibliographicCitation | JOURNAL OF CLINICAL PHARMACOLOGY, v.59, no.11, pp.1453 - 1461 | - |
dc.relation.isPartOf | JOURNAL OF CLINICAL PHARMACOLOGY | - |
dc.citation.title | JOURNAL OF CLINICAL PHARMACOLOGY | - |
dc.citation.volume | 59 | - |
dc.citation.number | 11 | - |
dc.citation.startPage | 1453 | - |
dc.citation.endPage | 1461 | - |
dc.type.rims | ART | - |
dc.type.docType | Article | - |
dc.description.journalClass | 1 | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
dc.relation.journalResearchArea | Pharmacology & Pharmacy | - |
dc.relation.journalWebOfScienceCategory | Pharmacology & Pharmacy | - |
dc.subject.keywordPlus | OMEGA-HYDROXYLATION | - |
dc.subject.keywordPlus | CHINESE PATIENTS | - |
dc.subject.keywordPlus | ISCHEMIC-STROKE | - |
dc.subject.keywordPlus | HUMAN LIVER | - |
dc.subject.keywordPlus | WARFARIN | - |
dc.subject.keywordPlus | VKORC1 | - |
dc.subject.keywordPlus | 20-HETE | - |
dc.subject.keywordPlus | ENZYMES | - |
dc.subject.keywordPlus | METABOLISM | - |
dc.subject.keywordPlus | VARIANT | - |
dc.subject.keywordAuthor | Vitamin K-1 | - |
dc.subject.keywordAuthor | warfarin | - |
dc.subject.keywordAuthor | pharmacogenetics | - |
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