Factor Xa inhibitors in clinical practice: Comparison of pharmacokinetic profiles

The anticoagulant actions of oral direct factor Xa (FXa) inhibitors can be inferred from their observed plasma concentrations; however, the steady-state pharmacokinetics (PK) of different FXa inhibitors have not been compared in clinically. The sensitivity of the rivaroxaban, apixaban, and edoxaban...

Full description

Saved in:
Bibliographic Details
Published in:Drug metabolism and pharmacokinetics 2020-02, Vol.35 (1), p.151-159
Main Authors: Goto, Eri, Horinaka, Shigeo, Ishimitsu, Toshihiko, Kato, Toru
Format: Article
Language:English
Subjects:
anti-FXa activity
Apixaban
Atrial fibrillation
Edoxaban
Plasma concentration
Population pharmacokinetics
Rivaroxaban
Venous thromboembolism
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
cited_by cdi_FETCH-LOGICAL-c490t-e1f48bdd2e45985e102422c0d1683d974b2b16b1fb14ab3a80088705ae1b04763
cites cdi_FETCH-LOGICAL-c490t-e1f48bdd2e45985e102422c0d1683d974b2b16b1fb14ab3a80088705ae1b04763
container_end_page 159
container_issue 1
container_start_page 151
container_title Drug metabolism and pharmacokinetics
container_volume 35
creator Goto, Eri
Horinaka, Shigeo
Ishimitsu, Toshihiko
Kato, Toru
description The anticoagulant actions of oral direct factor Xa (FXa) inhibitors can be inferred from their observed plasma concentrations; however, the steady-state pharmacokinetics (PK) of different FXa inhibitors have not been compared in clinically. The sensitivity of the rivaroxaban, apixaban, and edoxaban in the STA-Liquid Anti-FXa assay were compared, and the anti-FXa plasma concentrations were measured for PK assessments. Nonlinear mixed-effects modeling was used to assess population PK in 329 patients with nonvalvular atrial fibrillation or venous thromboembolism. Patients were followed up for an average of 3.6 years. Sensitivity was similar among the three drugs in this assay, which could directly compare plasma concentrations instead of anti-FXa activities. Overall exposure was greatest in 5 mg BID apixaban relative to other drugs (p 
doi_str_mv 10.1016/j.dmpk.2019.10.005
format article
fullrecord <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_2350338802</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><els_id>S1347436719300692</els_id><sourcerecordid>2350338802</sourcerecordid><originalsourceid>FETCH-LOGICAL-c490t-e1f48bdd2e45985e102422c0d1683d974b2b16b1fb14ab3a80088705ae1b04763</originalsourceid><addsrcrecordid>eNp9kE1LAzEQhoMotlb_gAfZo5etk4_9Ei9SrAoFERS8hSQ7S9PubtakFfz3prR69JTJ5Jk3zEPIJYUpBZrfrKZ1N6ynDGgVG1OA7IiMaVlCChWD41hzUaSC58WInIWwAuA8E-yUjDgDKGI9Jq9zZTbOJx8qsf3SahsvIZaJaW1vjWqTwUfCGrxNZq4blLfB9YlrkmGpfKeMW9se43vkXGNbDOfkpFFtwIvDOSHv84e32VO6eHl8nt0vUiMq2KRIG1HqumYosqrMkAITjBmoaV7yuiqEZprmmjaaCqW5KgHKsoBMIdUgipxPyPU-N378ucWwkZ0NBttW9ei2QTKexX2jDRZRtkeNdyF4bOTgbaf8t6QgdyrlSu5Uyp3KXS-qjENXh_yt7rD-G_l1F4G7PYBxyy-LXgZjsTdYW49mI2tn_8v_AbgfhIM</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2350338802</pqid></control><display><type>article</type><title>Factor Xa inhibitors in clinical practice: Comparison of pharmacokinetic profiles</title><source>ScienceDirect Freedom Collection</source><creator>Goto, Eri ; Horinaka, Shigeo ; Ishimitsu, Toshihiko ; Kato, Toru</creator><creatorcontrib>Goto, Eri ; Horinaka, Shigeo ; Ishimitsu, Toshihiko ; Kato, Toru</creatorcontrib><description>The anticoagulant actions of oral direct factor Xa (FXa) inhibitors can be inferred from their observed plasma concentrations; however, the steady-state pharmacokinetics (PK) of different FXa inhibitors have not been compared in clinically. The sensitivity of the rivaroxaban, apixaban, and edoxaban in the STA-Liquid Anti-FXa assay were compared, and the anti-FXa plasma concentrations were measured for PK assessments. Nonlinear mixed-effects modeling was used to assess population PK in 329 patients with nonvalvular atrial fibrillation or venous thromboembolism. Patients were followed up for an average of 3.6 years. Sensitivity was similar among the three drugs in this assay, which could directly compare plasma concentrations instead of anti-FXa activities. Overall exposure was greatest in 5 mg BID apixaban relative to other drugs (p &lt; 0.001). The geometric mean AUC for the 0 to 24-h interval was 4550 ng h/mL for apixaban, 2710 ng h/mL for 15 mg QD rivaroxaban, and 1290 ng h/mL for 60 mg QD edoxaban. The PKs of 2.5 mg BID apixaban or 15 mg QD rivaroxaban were associated with hemorrhagic events. Apixaban was associated with greater exposure, higher trough concentrations in plasma compared with rivaroxaban or edoxaban. Furthermore, a higher plasma concentration may partially predict hemorrhagic events. [Display omitted]</description><identifier>ISSN: 1347-4367</identifier><identifier>EISSN: 1880-0920</identifier><identifier>DOI: 10.1016/j.dmpk.2019.10.005</identifier><identifier>PMID: 32007354</identifier><language>eng</language><publisher>England: Elsevier Ltd</publisher><subject>anti-FXa activity ; Apixaban ; Atrial fibrillation ; Edoxaban ; Plasma concentration ; Population pharmacokinetics ; Rivaroxaban ; Venous thromboembolism</subject><ispartof>Drug metabolism and pharmacokinetics, 2020-02, Vol.35 (1), p.151-159</ispartof><rights>2019 The Japanese Society for the Study of Xenobiotics</rights><rights>Copyright © 2019 The Japanese Society for the Study of Xenobiotics. Published by Elsevier Ltd. All rights reserved.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c490t-e1f48bdd2e45985e102422c0d1683d974b2b16b1fb14ab3a80088705ae1b04763</citedby><cites>FETCH-LOGICAL-c490t-e1f48bdd2e45985e102422c0d1683d974b2b16b1fb14ab3a80088705ae1b04763</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/32007354$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Goto, Eri</creatorcontrib><creatorcontrib>Horinaka, Shigeo</creatorcontrib><creatorcontrib>Ishimitsu, Toshihiko</creatorcontrib><creatorcontrib>Kato, Toru</creatorcontrib><title>Factor Xa inhibitors in clinical practice: Comparison of pharmacokinetic profiles</title><title>Drug metabolism and pharmacokinetics</title><addtitle>Drug Metab Pharmacokinet</addtitle><description>The anticoagulant actions of oral direct factor Xa (FXa) inhibitors can be inferred from their observed plasma concentrations; however, the steady-state pharmacokinetics (PK) of different FXa inhibitors have not been compared in clinically. The sensitivity of the rivaroxaban, apixaban, and edoxaban in the STA-Liquid Anti-FXa assay were compared, and the anti-FXa plasma concentrations were measured for PK assessments. Nonlinear mixed-effects modeling was used to assess population PK in 329 patients with nonvalvular atrial fibrillation or venous thromboembolism. Patients were followed up for an average of 3.6 years. Sensitivity was similar among the three drugs in this assay, which could directly compare plasma concentrations instead of anti-FXa activities. Overall exposure was greatest in 5 mg BID apixaban relative to other drugs (p &lt; 0.001). The geometric mean AUC for the 0 to 24-h interval was 4550 ng h/mL for apixaban, 2710 ng h/mL for 15 mg QD rivaroxaban, and 1290 ng h/mL for 60 mg QD edoxaban. The PKs of 2.5 mg BID apixaban or 15 mg QD rivaroxaban were associated with hemorrhagic events. Apixaban was associated with greater exposure, higher trough concentrations in plasma compared with rivaroxaban or edoxaban. Furthermore, a higher plasma concentration may partially predict hemorrhagic events. [Display omitted]</description><subject>anti-FXa activity</subject><subject>Apixaban</subject><subject>Atrial fibrillation</subject><subject>Edoxaban</subject><subject>Plasma concentration</subject><subject>Population pharmacokinetics</subject><subject>Rivaroxaban</subject><subject>Venous thromboembolism</subject><issn>1347-4367</issn><issn>1880-0920</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><recordid>eNp9kE1LAzEQhoMotlb_gAfZo5etk4_9Ei9SrAoFERS8hSQ7S9PubtakFfz3prR69JTJ5Jk3zEPIJYUpBZrfrKZ1N6ynDGgVG1OA7IiMaVlCChWD41hzUaSC58WInIWwAuA8E-yUjDgDKGI9Jq9zZTbOJx8qsf3SahsvIZaJaW1vjWqTwUfCGrxNZq4blLfB9YlrkmGpfKeMW9se43vkXGNbDOfkpFFtwIvDOSHv84e32VO6eHl8nt0vUiMq2KRIG1HqumYosqrMkAITjBmoaV7yuiqEZprmmjaaCqW5KgHKsoBMIdUgipxPyPU-N378ucWwkZ0NBttW9ei2QTKexX2jDRZRtkeNdyF4bOTgbaf8t6QgdyrlSu5Uyp3KXS-qjENXh_yt7rD-G_l1F4G7PYBxyy-LXgZjsTdYW49mI2tn_8v_AbgfhIM</recordid><startdate>202002</startdate><enddate>202002</enddate><creator>Goto, Eri</creator><creator>Horinaka, Shigeo</creator><creator>Ishimitsu, Toshihiko</creator><creator>Kato, Toru</creator><general>Elsevier Ltd</general><scope>6I.</scope><scope>AAFTH</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>202002</creationdate><title>Factor Xa inhibitors in clinical practice: Comparison of pharmacokinetic profiles</title><author>Goto, Eri ; Horinaka, Shigeo ; Ishimitsu, Toshihiko ; Kato, Toru</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c490t-e1f48bdd2e45985e102422c0d1683d974b2b16b1fb14ab3a80088705ae1b04763</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>anti-FXa activity</topic><topic>Apixaban</topic><topic>Atrial fibrillation</topic><topic>Edoxaban</topic><topic>Plasma concentration</topic><topic>Population pharmacokinetics</topic><topic>Rivaroxaban</topic><topic>Venous thromboembolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Goto, Eri</creatorcontrib><creatorcontrib>Horinaka, Shigeo</creatorcontrib><creatorcontrib>Ishimitsu, Toshihiko</creatorcontrib><creatorcontrib>Kato, Toru</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Drug metabolism and pharmacokinetics</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Goto, Eri</au><au>Horinaka, Shigeo</au><au>Ishimitsu, Toshihiko</au><au>Kato, Toru</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Factor Xa inhibitors in clinical practice: Comparison of pharmacokinetic profiles</atitle><jtitle>Drug metabolism and pharmacokinetics</jtitle><addtitle>Drug Metab Pharmacokinet</addtitle><date>2020-02</date><risdate>2020</risdate><volume>35</volume><issue>1</issue><spage>151</spage><epage>159</epage><pages>151-159</pages><issn>1347-4367</issn><eissn>1880-0920</eissn><abstract>The anticoagulant actions of oral direct factor Xa (FXa) inhibitors can be inferred from their observed plasma concentrations; however, the steady-state pharmacokinetics (PK) of different FXa inhibitors have not been compared in clinically. The sensitivity of the rivaroxaban, apixaban, and edoxaban in the STA-Liquid Anti-FXa assay were compared, and the anti-FXa plasma concentrations were measured for PK assessments. Nonlinear mixed-effects modeling was used to assess population PK in 329 patients with nonvalvular atrial fibrillation or venous thromboembolism. Patients were followed up for an average of 3.6 years. Sensitivity was similar among the three drugs in this assay, which could directly compare plasma concentrations instead of anti-FXa activities. Overall exposure was greatest in 5 mg BID apixaban relative to other drugs (p &lt; 0.001). The geometric mean AUC for the 0 to 24-h interval was 4550 ng h/mL for apixaban, 2710 ng h/mL for 15 mg QD rivaroxaban, and 1290 ng h/mL for 60 mg QD edoxaban. The PKs of 2.5 mg BID apixaban or 15 mg QD rivaroxaban were associated with hemorrhagic events. Apixaban was associated with greater exposure, higher trough concentrations in plasma compared with rivaroxaban or edoxaban. Furthermore, a higher plasma concentration may partially predict hemorrhagic events. [Display omitted]</abstract><cop>England</cop><pub>Elsevier Ltd</pub><pmid>32007354</pmid><doi>10.1016/j.dmpk.2019.10.005</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record>
fulltext fulltext
identifier ISSN: 1347-4367
ispartof Drug metabolism and pharmacokinetics, 2020-02, Vol.35 (1), p.151-159
issn 1347-4367
1880-0920
language eng
recordid cdi_proquest_miscellaneous_2350338802
source ScienceDirect Freedom Collection
subjects anti-FXa activity
Apixaban
Atrial fibrillation
Edoxaban
Plasma concentration
Population pharmacokinetics
Rivaroxaban
Venous thromboembolism
title Factor Xa inhibitors in clinical practice: Comparison of pharmacokinetic profiles
url http://sfxeu10.hosted.exlibrisgroup.com/loughborough?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-08T06%3A17%3A22IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Factor%20Xa%20inhibitors%20in%20clinical%20practice:%20Comparison%20of%20pharmacokinetic%20profiles&rft.jtitle=Drug%20metabolism%20and%20pharmacokinetics&rft.au=Goto,%20Eri&rft.date=2020-02&rft.volume=35&rft.issue=1&rft.spage=151&rft.epage=159&rft.pages=151-159&rft.issn=1347-4367&rft.eissn=1880-0920&rft_id=info:doi/10.1016/j.dmpk.2019.10.005&rft_dat=%3Cproquest_cross%3E2350338802%3C/proquest_cross%3E%3Cgrp_id%3Ecdi_FETCH-LOGICAL-c490t-e1f48bdd2e45985e102422c0d1683d974b2b16b1fb14ab3a80088705ae1b04763%3C/grp_id%3E%3Coa%3E%3C/oa%3E%3Curl%3E%3C/url%3E&rft_id=info:oai/&rft_pqid=2350338802&rft_id=info:pmid/32007354&rfr_iscdi=true