Effects of verapamil and diltiazem on the pharmacokinetics and pharmacodynamics of rivaroxaban
DC Field | Value | Language |
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dc.contributor.author | Kim, M. | - |
dc.contributor.author | Son, H. | - |
dc.contributor.author | Noh, K. | - |
dc.contributor.author | Kim, E. | - |
dc.contributor.author | Shin, B. | - |
dc.contributor.author | Kang, W. | - |
dc.date.available | 2019-08-30T03:01:36Z | - |
dc.date.issued | 2019-03 | - |
dc.identifier.issn | 1999-4923 | - |
dc.identifier.issn | 1999-4923 | - |
dc.identifier.uri | https://scholarworks.bwise.kr/cau/handle/2019.sw.cau/36498 | - |
dc.description.abstract | Concomitant use of rivaroxaban with non-dihydropyridine calcium channel blockers (non-DHPs) might lead to an increase of systemic rivaroxaban exposure and anticoagulant effects in relation to the inhibition of metabolic enzymes and/or transporters by non-DHPs. This study was designed to evaluate the effects of verapamil and diltiazem on the pharmacokinetics and the prolongation of prothrombin time of rivaroxaban in rats. The data were analyzed using a pharmacokinetic/pharmacodynamics (PK/PD) modeling approach to quantify the influence of verapamil. Verapamil increased the systemic exposure of rivaroxaban by 2.8-fold (p <0.001) which was probably due to the inhibition of efflux transportation rather than metabolism. Prothrombin time was also prolonged in a proportional manner; diltiazem did not show any significant effects, however. A transit PK model in the absorption process comprehensively describes the double-peaks of rivaroxaban plasma concentrations and the corresponding change of prothrombin time with a simple linear relationship. The slope of prothrombin time vs. rivaroxaban plasma concentration in rats was retrospectively found to be insensitive by about 5.4-fold compared to than in humans. More than a 67% dose reduction in rivaroxaban is suggested in terms of both a pharmacokinetic point of view, and the sensitivity differences on the prolongation of prothrombin time when used concomitantly with verapamil. © 2019 by the authors. Licensee MDPI, Basel, Switzerland. | - |
dc.format.extent | 10 | - |
dc.language | 영어 | - |
dc.language.iso | ENG | - |
dc.publisher | MDPI AG | - |
dc.title | Effects of verapamil and diltiazem on the pharmacokinetics and pharmacodynamics of rivaroxaban | - |
dc.type | Article | - |
dc.identifier.doi | 10.3390/pharmaceutics11030133 | - |
dc.identifier.bibliographicCitation | Pharmaceutics, v.11, no.3, pp 1 - 10 | - |
dc.description.isOpenAccess | N | - |
dc.identifier.wosid | 000466897800035 | - |
dc.identifier.scopusid | 2-s2.0-85069535902 | - |
dc.citation.endPage | 10 | - |
dc.citation.number | 3 | - |
dc.citation.startPage | 1 | - |
dc.citation.title | Pharmaceutics | - |
dc.citation.volume | 11 | - |
dc.type.docType | Article | - |
dc.publisher.location | 스위스 | - |
dc.subject.keywordAuthor | Drug–drug interaction | - |
dc.subject.keywordAuthor | PK/PD modeling | - |
dc.subject.keywordAuthor | Prothrombin time | - |
dc.subject.keywordAuthor | Rivaroxaban | - |
dc.subject.keywordAuthor | Verapamil | - |
dc.subject.keywordPlus | blood clotting factor 10a | - |
dc.subject.keywordPlus | diltiazem | - |
dc.subject.keywordPlus | rivaroxaban | - |
dc.subject.keywordPlus | verapamil | - |
dc.subject.keywordPlus | animal experiment | - |
dc.subject.keywordPlus | area under the curve | - |
dc.subject.keywordPlus | Article | - |
dc.subject.keywordPlus | controlled study | - |
dc.subject.keywordPlus | drug absorption | - |
dc.subject.keywordPlus | drug clearance | - |
dc.subject.keywordPlus | drug disposition | - |
dc.subject.keywordPlus | drug half life | - |
dc.subject.keywordPlus | drug metabolism | - |
dc.subject.keywordPlus | drug potentiation | - |
dc.subject.keywordPlus | maximum concentration | - |
dc.subject.keywordPlus | Monte Carlo method | - |
dc.subject.keywordPlus | nonhuman | - |
dc.subject.keywordPlus | prothrombin time | - |
dc.subject.keywordPlus | rat | - |
dc.relation.journalResearchArea | Pharmacology & Pharmacy | - |
dc.relation.journalWebOfScienceCategory | Pharmacology & Pharmacy | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
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