Negative Food Effect of Danirixin: Use of PBPK Modelling to Explore the Effect of Formulation and Meal Type on Clinical PK
Purpose To use physiologically-based pharmacokinetic (PBPK) modelling to explore the food effect of different DNX hydrobromide (HBr) hemihydrate salt tablet formulations using biorelevant dissolution. Methods Compendial dissolution using a paddle method and TIM-1 biorelevant dissolution were perform...
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| Veröffentlicht in: | Pharmaceutical research 2020-12, Vol.37 (12), p.233-233, Article 233 |
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| creator | Lloyd, Richard S. Hingle, Martin I. Bloomer, Jackie C. Charles, Stephen J. Butler, James M. Paul, Alan Zhu, Xiaofeng Miller, Bruce D’Amico, Donald Donald, Alison Tal-Singer, Ruth Ambery, Claire |
| description | Purpose
To use physiologically-based pharmacokinetic (PBPK) modelling to explore the food effect of different DNX hydrobromide (HBr) hemihydrate salt tablet formulations using biorelevant dissolution.
Methods
Compendial dissolution using a paddle method and TIM-1 biorelevant dissolution were performed and incorporated into a previously reported PBPK model. A two-part clinical study evaluated tablet formulations in the fasted/fed (high fat) state (Part A), and the impact of food (fasted/normal/high fat) and Proton Pump Inhibitor (PPI) co-administration for a selected formulation; as well as a formulation containing DNX HBr in the monohydrate state (Part B).
Results
TIM-1 data showed that the fed state bioaccessibility of DNX was significantly decreased compared to the fasted state with no significant differences between formulations. Dosed with normal/high fat food the selected formulation showed comparable exposure and a modest increase in DNX systemic PK was observed with PPI dependent on meal type. Under fed conditions DNX systemic exposure was comparable for the monohydrate and hemihydrate formulations. The integration of biorelevant TIM-1 data into the PBPK model led to the successful simulation of a DNX negative food effect.
Conclusions
Interactions between DNX and food components are the likely the source of the negative food effect via micellar entrapment, ion pairing and/or meal induced viscosity changes. |
| doi_str_mv | 10.1007/s11095-020-02948-z |
| format | Article |
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To use physiologically-based pharmacokinetic (PBPK) modelling to explore the food effect of different DNX hydrobromide (HBr) hemihydrate salt tablet formulations using biorelevant dissolution.
Methods
Compendial dissolution using a paddle method and TIM-1 biorelevant dissolution were performed and incorporated into a previously reported PBPK model. A two-part clinical study evaluated tablet formulations in the fasted/fed (high fat) state (Part A), and the impact of food (fasted/normal/high fat) and Proton Pump Inhibitor (PPI) co-administration for a selected formulation; as well as a formulation containing DNX HBr in the monohydrate state (Part B).
Results
TIM-1 data showed that the fed state bioaccessibility of DNX was significantly decreased compared to the fasted state with no significant differences between formulations. Dosed with normal/high fat food the selected formulation showed comparable exposure and a modest increase in DNX systemic PK was observed with PPI dependent on meal type. Under fed conditions DNX systemic exposure was comparable for the monohydrate and hemihydrate formulations. The integration of biorelevant TIM-1 data into the PBPK model led to the successful simulation of a DNX negative food effect.
Conclusions
Interactions between DNX and food components are the likely the source of the negative food effect via micellar entrapment, ion pairing and/or meal induced viscosity changes.</description><identifier>ISSN: 0724-8741</identifier><identifier>EISSN: 1573-904X</identifier><identifier>DOI: 10.1007/s11095-020-02948-z</identifier><identifier>PMID: 33123802</identifier><language>eng</language><publisher>New York: Springer US</publisher><subject>Biochemistry ; Biomedical and Life Sciences ; Biomedical Engineering and Bioengineering ; Biomedicine ; Dissolution ; Food ; Food selection ; Medical Law ; Pharmacokinetics ; Pharmacology/Toxicology ; Pharmacy ; Proton pump inhibitors ; Research Paper</subject><ispartof>Pharmaceutical research, 2020-12, Vol.37 (12), p.233-233, Article 233</ispartof><rights>Springer Science+Business Media, LLC, part of Springer Nature 2020</rights><rights>COPYRIGHT 2020 Springer</rights><rights>Springer Science+Business Media, LLC, part of Springer Nature 2020.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c414t-8b2868d5843dd08f4b43c52a179774cc9ada00f0cded5b7cef22a402557232553</citedby><cites>FETCH-LOGICAL-c414t-8b2868d5843dd08f4b43c52a179774cc9ada00f0cded5b7cef22a402557232553</cites><orcidid>0000-0002-7988-1888</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s11095-020-02948-z$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s11095-020-02948-z$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,776,780,27901,27902,41464,42533,51294</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33123802$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Lloyd, Richard S.</creatorcontrib><creatorcontrib>Hingle, Martin I.</creatorcontrib><creatorcontrib>Bloomer, Jackie C.</creatorcontrib><creatorcontrib>Charles, Stephen J.</creatorcontrib><creatorcontrib>Butler, James M.</creatorcontrib><creatorcontrib>Paul, Alan</creatorcontrib><creatorcontrib>Zhu, Xiaofeng</creatorcontrib><creatorcontrib>Miller, Bruce</creatorcontrib><creatorcontrib>D’Amico, Donald</creatorcontrib><creatorcontrib>Donald, Alison</creatorcontrib><creatorcontrib>Tal-Singer, Ruth</creatorcontrib><creatorcontrib>Ambery, Claire</creatorcontrib><title>Negative Food Effect of Danirixin: Use of PBPK Modelling to Explore the Effect of Formulation and Meal Type on Clinical PK</title><title>Pharmaceutical research</title><addtitle>Pharm Res</addtitle><addtitle>Pharm Res</addtitle><description>Purpose
To use physiologically-based pharmacokinetic (PBPK) modelling to explore the food effect of different DNX hydrobromide (HBr) hemihydrate salt tablet formulations using biorelevant dissolution.
Methods
Compendial dissolution using a paddle method and TIM-1 biorelevant dissolution were performed and incorporated into a previously reported PBPK model. A two-part clinical study evaluated tablet formulations in the fasted/fed (high fat) state (Part A), and the impact of food (fasted/normal/high fat) and Proton Pump Inhibitor (PPI) co-administration for a selected formulation; as well as a formulation containing DNX HBr in the monohydrate state (Part B).
Results
TIM-1 data showed that the fed state bioaccessibility of DNX was significantly decreased compared to the fasted state with no significant differences between formulations. Dosed with normal/high fat food the selected formulation showed comparable exposure and a modest increase in DNX systemic PK was observed with PPI dependent on meal type. Under fed conditions DNX systemic exposure was comparable for the monohydrate and hemihydrate formulations. The integration of biorelevant TIM-1 data into the PBPK model led to the successful simulation of a DNX negative food effect.
Conclusions
Interactions between DNX and food components are the likely the source of the negative food effect via micellar entrapment, ion pairing and/or meal induced viscosity changes.</description><subject>Biochemistry</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedical Engineering and Bioengineering</subject><subject>Biomedicine</subject><subject>Dissolution</subject><subject>Food</subject><subject>Food selection</subject><subject>Medical Law</subject><subject>Pharmacokinetics</subject><subject>Pharmacology/Toxicology</subject><subject>Pharmacy</subject><subject>Proton pump inhibitors</subject><subject>Research Paper</subject><issn>0724-8741</issn><issn>1573-904X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>BENPR</sourceid><recordid>eNp9kctuEzEYhS1ERUPhBVggS2zYTOtr7WFXQgKoLWTRSuwsx5fgasYO9gxq8_Q4TGkRC2TZln6f7-hYB4BXGB1jhMRJwRi1vEEE1d0y2eyegBnmgjYtYt-eghkShDVSMHwInpdygxCSuGXPwCGlmFCJyAzsvriNHsJPB5cpWbjw3pkBJg8_6BhyuA3xHbwubj9ZvV-dw8tkXdeFuIFDgovbbZeyg8N39xe5TLkfu2qaItTRwkunO3h1t60mEc4rG0wdrM5fgAOvu-Je3t9H4Hq5uJp_ai6-fvw8P7toDMNsaOSayFNpuWTUWiQ9WzNqONFYtEIwY1ptNUIeGessXwvjPCGaIcK5ILSe9Ai8nXy3Of0YXRlUH4qpv9DRpbEowvgpw5xxWaVv_pHepDHHmq6qBBZSCrw3PJ5UG905FaJPQ9amLuv6YFJ0PtT5mWCC0Ra3uAJkAkxOpWTn1TaHXuc7hZHaV6mmKlWtUv2uUu0q9Po-y7junX1A_nRXBXQSlPoUNy4_hv2P7S8l26eM</recordid><startdate>20201201</startdate><enddate>20201201</enddate><creator>Lloyd, Richard S.</creator><creator>Hingle, Martin I.</creator><creator>Bloomer, Jackie C.</creator><creator>Charles, Stephen J.</creator><creator>Butler, James M.</creator><creator>Paul, Alan</creator><creator>Zhu, Xiaofeng</creator><creator>Miller, Bruce</creator><creator>D’Amico, Donald</creator><creator>Donald, Alison</creator><creator>Tal-Singer, Ruth</creator><creator>Ambery, Claire</creator><general>Springer US</general><general>Springer</general><general>Springer Nature B.V</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7RV</scope><scope>7TK</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>K9.</scope><scope>KB0</scope><scope>M0S</scope><scope>M1P</scope><scope>NAPCQ</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0002-7988-1888</orcidid></search><sort><creationdate>20201201</creationdate><title>Negative Food Effect of Danirixin: Use of PBPK Modelling to Explore the Effect of Formulation and Meal Type on Clinical PK</title><author>Lloyd, Richard S. ; Hingle, Martin I. ; Bloomer, Jackie C. ; Charles, Stephen J. ; Butler, James M. ; Paul, Alan ; Zhu, Xiaofeng ; Miller, Bruce ; D’Amico, Donald ; Donald, Alison ; Tal-Singer, Ruth ; Ambery, Claire</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c414t-8b2868d5843dd08f4b43c52a179774cc9ada00f0cded5b7cef22a402557232553</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Biochemistry</topic><topic>Biomedical and Life Sciences</topic><topic>Biomedical Engineering and Bioengineering</topic><topic>Biomedicine</topic><topic>Dissolution</topic><topic>Food</topic><topic>Food selection</topic><topic>Medical Law</topic><topic>Pharmacokinetics</topic><topic>Pharmacology/Toxicology</topic><topic>Pharmacy</topic><topic>Proton pump inhibitors</topic><topic>Research Paper</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Lloyd, Richard S.</creatorcontrib><creatorcontrib>Hingle, Martin I.</creatorcontrib><creatorcontrib>Bloomer, Jackie C.</creatorcontrib><creatorcontrib>Charles, Stephen J.</creatorcontrib><creatorcontrib>Butler, James M.</creatorcontrib><creatorcontrib>Paul, Alan</creatorcontrib><creatorcontrib>Zhu, Xiaofeng</creatorcontrib><creatorcontrib>Miller, Bruce</creatorcontrib><creatorcontrib>D’Amico, Donald</creatorcontrib><creatorcontrib>Donald, Alison</creatorcontrib><creatorcontrib>Tal-Singer, Ruth</creatorcontrib><creatorcontrib>Ambery, Claire</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Nursing & Allied Health Database</collection><collection>Neurosciences Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Nursing & Allied Health Premium</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>MEDLINE - Academic</collection><jtitle>Pharmaceutical research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Lloyd, Richard S.</au><au>Hingle, Martin I.</au><au>Bloomer, Jackie C.</au><au>Charles, Stephen J.</au><au>Butler, James M.</au><au>Paul, Alan</au><au>Zhu, Xiaofeng</au><au>Miller, Bruce</au><au>D’Amico, Donald</au><au>Donald, Alison</au><au>Tal-Singer, Ruth</au><au>Ambery, Claire</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Negative Food Effect of Danirixin: Use of PBPK Modelling to Explore the Effect of Formulation and Meal Type on Clinical PK</atitle><jtitle>Pharmaceutical research</jtitle><stitle>Pharm Res</stitle><addtitle>Pharm Res</addtitle><date>2020-12-01</date><risdate>2020</risdate><volume>37</volume><issue>12</issue><spage>233</spage><epage>233</epage><pages>233-233</pages><artnum>233</artnum><issn>0724-8741</issn><eissn>1573-904X</eissn><abstract>Purpose
To use physiologically-based pharmacokinetic (PBPK) modelling to explore the food effect of different DNX hydrobromide (HBr) hemihydrate salt tablet formulations using biorelevant dissolution.
Methods
Compendial dissolution using a paddle method and TIM-1 biorelevant dissolution were performed and incorporated into a previously reported PBPK model. A two-part clinical study evaluated tablet formulations in the fasted/fed (high fat) state (Part A), and the impact of food (fasted/normal/high fat) and Proton Pump Inhibitor (PPI) co-administration for a selected formulation; as well as a formulation containing DNX HBr in the monohydrate state (Part B).
Results
TIM-1 data showed that the fed state bioaccessibility of DNX was significantly decreased compared to the fasted state with no significant differences between formulations. Dosed with normal/high fat food the selected formulation showed comparable exposure and a modest increase in DNX systemic PK was observed with PPI dependent on meal type. Under fed conditions DNX systemic exposure was comparable for the monohydrate and hemihydrate formulations. The integration of biorelevant TIM-1 data into the PBPK model led to the successful simulation of a DNX negative food effect.
Conclusions
Interactions between DNX and food components are the likely the source of the negative food effect via micellar entrapment, ion pairing and/or meal induced viscosity changes.</abstract><cop>New York</cop><pub>Springer US</pub><pmid>33123802</pmid><doi>10.1007/s11095-020-02948-z</doi><tpages>1</tpages><orcidid>https://orcid.org/0000-0002-7988-1888</orcidid></addata></record> |
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| language | eng |
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| source | Springer Nature - Complete Springer Journals |
| subjects | Biochemistry Biomedical and Life Sciences Biomedical Engineering and Bioengineering Biomedicine Dissolution Food Food selection Medical Law Pharmacokinetics Pharmacology/Toxicology Pharmacy Proton pump inhibitors Research Paper |
| title | Negative Food Effect of Danirixin: Use of PBPK Modelling to Explore the Effect of Formulation and Meal Type on Clinical PK |
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