Effect of resveratrol on the pharmacokinetics of fexofenadine in rats: Involvement of P-glycoprotein inhibition
Resveratrol (RSV) is a natural occurring antioxidant has been found to possess P-glycoprotein (P-gp) inhibition activity in vitro and in vivo, which may have the potential to cause drug–phytochemical interactions. The purpose of the present study was to evaluate the effect of RSV on the pharmacokine...
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| Veröffentlicht in: | Pharmacological reports 2016-04, Vol.68 (2), p.338-343 |
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| creator | Bedada, Satish Kumar Yellu, Narsimha Reddy Neerati, Prasad |
| description | Resveratrol (RSV) is a natural occurring antioxidant has been found to possess P-glycoprotein (P-gp) inhibition activity in vitro and in vivo, which may have the potential to cause drug–phytochemical interactions. The purpose of the present study was to evaluate the effect of RSV on the pharmacokinetics of fexofenadine (FEX), P-gp substrate in rats.
A mechanistic evaluation was undertaken using in vitro non-everted sac and in situ intestinal perfusion studies to determine the FEX intestinal transport and permeability. These results were confirmed by an in vivo pharmacokinetic study of oral administered FEX (10mg/kg) in rats.
The intestinal transport and apparent permeability (Papp) of FEX were increased significantly in duodenum, jejunum and ileum of RSV and verapamil (VER) pretreated groups when compared to FEX alone group. Similarly absorption rate constant (Ka), fraction absorbed (Fab) and effective permeability (Peff) of FEX were increased significantly in ileum of RSV and VER pretreated groups when compared to FEX alone group. In comparison with FEX alone, RSV pretreatment significantly increased maximum plasma concentration (Cmax) and area under the concentration–time curve (AUC), while there was no significant change was observed in T1/2 and Tmax of FEX.
RSV significantly enhanced the exposure of FEX in rats likely by the inhibition of P-glycoprotein (P-gp) mediated efflux during the intestinal absorption, suggesting that there is a potential pharmacokinetic interaction between RSV and FEX. Therefore, further studies are recommended to evaluate the potential drug–phytochemical interactions in humans. |
| doi_str_mv | 10.1016/j.pharep.2015.08.018 |
| format | Article |
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A mechanistic evaluation was undertaken using in vitro non-everted sac and in situ intestinal perfusion studies to determine the FEX intestinal transport and permeability. These results were confirmed by an in vivo pharmacokinetic study of oral administered FEX (10mg/kg) in rats.
The intestinal transport and apparent permeability (Papp) of FEX were increased significantly in duodenum, jejunum and ileum of RSV and verapamil (VER) pretreated groups when compared to FEX alone group. Similarly absorption rate constant (Ka), fraction absorbed (Fab) and effective permeability (Peff) of FEX were increased significantly in ileum of RSV and VER pretreated groups when compared to FEX alone group. In comparison with FEX alone, RSV pretreatment significantly increased maximum plasma concentration (Cmax) and area under the concentration–time curve (AUC), while there was no significant change was observed in T1/2 and Tmax of FEX.
RSV significantly enhanced the exposure of FEX in rats likely by the inhibition of P-glycoprotein (P-gp) mediated efflux during the intestinal absorption, suggesting that there is a potential pharmacokinetic interaction between RSV and FEX. Therefore, further studies are recommended to evaluate the potential drug–phytochemical interactions in humans.</description><identifier>ISSN: 1734-1140</identifier><identifier>EISSN: 2299-5684</identifier><identifier>DOI: 10.1016/j.pharep.2015.08.018</identifier><identifier>PMID: 26922536</identifier><language>eng</language><publisher>Cham: Elsevier Urban & Partner Sp. z o.o</publisher><subject>Administration, Oral ; Animals ; ATP Binding Cassette Transporter, Subfamily B - antagonists & inhibitors ; Biological Transport - drug effects ; Drug Interactions ; Drug Safety and Pharmacovigilance ; Drug–phytochemical interactions ; Fexofenadine ; Intestinal Absorption - drug effects ; Intestinal Mucosa - metabolism ; Intestines - drug effects ; Male ; Original Research Article ; P-glycoprotein ; Permeability - drug effects ; Pharmacokinetics ; Pharmacotherapy ; Pharmacy ; Rats ; Rats, Wistar ; Resveratrol ; Stilbenes - pharmacology ; Terfenadine - analogs & derivatives ; Terfenadine - pharmacokinetics ; Verapamil - pharmacology</subject><ispartof>Pharmacological reports, 2016-04, Vol.68 (2), p.338-343</ispartof><rights>2015 Institute of Pharmacology, Polish Academy of Sciences</rights><rights>Maj Institute of Pharmacology, Polish Academy of Sciences 2015</rights><rights>Copyright © 2015 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c408t-657745b7c17719f75f3ec8ea3cb58d636654edf65c8c8a73aa594d9537dcf0753</citedby><cites>FETCH-LOGICAL-c408t-657745b7c17719f75f3ec8ea3cb58d636654edf65c8c8a73aa594d9537dcf0753</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1016/j.pharep.2015.08.018$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1016/j.pharep.2015.08.018$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,780,784,27924,27925,41488,42557,51319</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26922536$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Bedada, Satish Kumar</creatorcontrib><creatorcontrib>Yellu, Narsimha Reddy</creatorcontrib><creatorcontrib>Neerati, Prasad</creatorcontrib><title>Effect of resveratrol on the pharmacokinetics of fexofenadine in rats: Involvement of P-glycoprotein inhibition</title><title>Pharmacological reports</title><addtitle>Pharmacol. Rep</addtitle><addtitle>Pharmacol Rep</addtitle><description>Resveratrol (RSV) is a natural occurring antioxidant has been found to possess P-glycoprotein (P-gp) inhibition activity in vitro and in vivo, which may have the potential to cause drug–phytochemical interactions. The purpose of the present study was to evaluate the effect of RSV on the pharmacokinetics of fexofenadine (FEX), P-gp substrate in rats.
A mechanistic evaluation was undertaken using in vitro non-everted sac and in situ intestinal perfusion studies to determine the FEX intestinal transport and permeability. These results were confirmed by an in vivo pharmacokinetic study of oral administered FEX (10mg/kg) in rats.
The intestinal transport and apparent permeability (Papp) of FEX were increased significantly in duodenum, jejunum and ileum of RSV and verapamil (VER) pretreated groups when compared to FEX alone group. Similarly absorption rate constant (Ka), fraction absorbed (Fab) and effective permeability (Peff) of FEX were increased significantly in ileum of RSV and VER pretreated groups when compared to FEX alone group. In comparison with FEX alone, RSV pretreatment significantly increased maximum plasma concentration (Cmax) and area under the concentration–time curve (AUC), while there was no significant change was observed in T1/2 and Tmax of FEX.
RSV significantly enhanced the exposure of FEX in rats likely by the inhibition of P-glycoprotein (P-gp) mediated efflux during the intestinal absorption, suggesting that there is a potential pharmacokinetic interaction between RSV and FEX. Therefore, further studies are recommended to evaluate the potential drug–phytochemical interactions in humans.</description><subject>Administration, Oral</subject><subject>Animals</subject><subject>ATP Binding Cassette Transporter, Subfamily B - antagonists & inhibitors</subject><subject>Biological Transport - drug effects</subject><subject>Drug Interactions</subject><subject>Drug Safety and Pharmacovigilance</subject><subject>Drug–phytochemical interactions</subject><subject>Fexofenadine</subject><subject>Intestinal Absorption - drug effects</subject><subject>Intestinal Mucosa - metabolism</subject><subject>Intestines - drug effects</subject><subject>Male</subject><subject>Original Research Article</subject><subject>P-glycoprotein</subject><subject>Permeability - drug effects</subject><subject>Pharmacokinetics</subject><subject>Pharmacotherapy</subject><subject>Pharmacy</subject><subject>Rats</subject><subject>Rats, Wistar</subject><subject>Resveratrol</subject><subject>Stilbenes - pharmacology</subject><subject>Terfenadine - analogs & derivatives</subject><subject>Terfenadine - pharmacokinetics</subject><subject>Verapamil - pharmacology</subject><issn>1734-1140</issn><issn>2299-5684</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkU9PHCEYh0lTU1fbb9A0c-xlRhj-Tg8mZmPVxEQPeiYs8-KynYEtzG7qt5d1rMf2RALP7_fCA0JfCW4IJuJs02zXJsG2aTHhDVYNJuoDWrRt19VcKPYRLYikrCaE4WN0kvMGY0Zayj-h41Z0bcupWKB46RzYqYquSpD3kMyU4lDFUE1rqA4TRmPjLx9g8jYfMAd_ooNg-rJX-VCVRP5R3YR9HPYwQnjtuq-fhmcbtylOUBgf1n7lJx_DZ3TkzJDhy9t6ih5_Xj4sr-vbu6ub5cVtbRlWUy24lIyvpCVSks5J7ihYBYbaFVe9oEJwBr0T3CqrjKTG8I71Haeytw5LTk_R97m3XOH3DvKkR58tDIMJEHdZEyk60VIlaEHZjNoUc07g9Db50aRnTbA-qNYbPavWB9UaK11Ul9i3twm71Qj9e-iv2wLwGcjlKDxB0pu4S6G8-n_F53MOip-9L7lsPQQLvU_lq3Qf_b8LXgDwAqUo</recordid><startdate>20160401</startdate><enddate>20160401</enddate><creator>Bedada, Satish Kumar</creator><creator>Yellu, Narsimha Reddy</creator><creator>Neerati, Prasad</creator><general>Elsevier Urban & Partner Sp. z o.o</general><general>Springer International Publishing</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>20160401</creationdate><title>Effect of resveratrol on the pharmacokinetics of fexofenadine in rats: Involvement of P-glycoprotein inhibition</title><author>Bedada, Satish Kumar ; Yellu, Narsimha Reddy ; Neerati, Prasad</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c408t-657745b7c17719f75f3ec8ea3cb58d636654edf65c8c8a73aa594d9537dcf0753</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>Administration, Oral</topic><topic>Animals</topic><topic>ATP Binding Cassette Transporter, Subfamily B - antagonists & inhibitors</topic><topic>Biological Transport - drug effects</topic><topic>Drug Interactions</topic><topic>Drug Safety and Pharmacovigilance</topic><topic>Drug–phytochemical interactions</topic><topic>Fexofenadine</topic><topic>Intestinal Absorption - drug effects</topic><topic>Intestinal Mucosa - metabolism</topic><topic>Intestines - drug effects</topic><topic>Male</topic><topic>Original Research Article</topic><topic>P-glycoprotein</topic><topic>Permeability - drug effects</topic><topic>Pharmacokinetics</topic><topic>Pharmacotherapy</topic><topic>Pharmacy</topic><topic>Rats</topic><topic>Rats, Wistar</topic><topic>Resveratrol</topic><topic>Stilbenes - pharmacology</topic><topic>Terfenadine - analogs & derivatives</topic><topic>Terfenadine - pharmacokinetics</topic><topic>Verapamil - pharmacology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Bedada, Satish Kumar</creatorcontrib><creatorcontrib>Yellu, Narsimha Reddy</creatorcontrib><creatorcontrib>Neerati, Prasad</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Pharmacological reports</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Bedada, Satish Kumar</au><au>Yellu, Narsimha Reddy</au><au>Neerati, Prasad</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Effect of resveratrol on the pharmacokinetics of fexofenadine in rats: Involvement of P-glycoprotein inhibition</atitle><jtitle>Pharmacological reports</jtitle><stitle>Pharmacol. Rep</stitle><addtitle>Pharmacol Rep</addtitle><date>2016-04-01</date><risdate>2016</risdate><volume>68</volume><issue>2</issue><spage>338</spage><epage>343</epage><pages>338-343</pages><issn>1734-1140</issn><eissn>2299-5684</eissn><abstract>Resveratrol (RSV) is a natural occurring antioxidant has been found to possess P-glycoprotein (P-gp) inhibition activity in vitro and in vivo, which may have the potential to cause drug–phytochemical interactions. The purpose of the present study was to evaluate the effect of RSV on the pharmacokinetics of fexofenadine (FEX), P-gp substrate in rats.
A mechanistic evaluation was undertaken using in vitro non-everted sac and in situ intestinal perfusion studies to determine the FEX intestinal transport and permeability. These results were confirmed by an in vivo pharmacokinetic study of oral administered FEX (10mg/kg) in rats.
The intestinal transport and apparent permeability (Papp) of FEX were increased significantly in duodenum, jejunum and ileum of RSV and verapamil (VER) pretreated groups when compared to FEX alone group. Similarly absorption rate constant (Ka), fraction absorbed (Fab) and effective permeability (Peff) of FEX were increased significantly in ileum of RSV and VER pretreated groups when compared to FEX alone group. In comparison with FEX alone, RSV pretreatment significantly increased maximum plasma concentration (Cmax) and area under the concentration–time curve (AUC), while there was no significant change was observed in T1/2 and Tmax of FEX.
RSV significantly enhanced the exposure of FEX in rats likely by the inhibition of P-glycoprotein (P-gp) mediated efflux during the intestinal absorption, suggesting that there is a potential pharmacokinetic interaction between RSV and FEX. Therefore, further studies are recommended to evaluate the potential drug–phytochemical interactions in humans.</abstract><cop>Cham</cop><pub>Elsevier Urban & Partner Sp. z o.o</pub><pmid>26922536</pmid><doi>10.1016/j.pharep.2015.08.018</doi><tpages>6</tpages></addata></record> |
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| subjects | Administration, Oral Animals ATP Binding Cassette Transporter, Subfamily B - antagonists & inhibitors Biological Transport - drug effects Drug Interactions Drug Safety and Pharmacovigilance Drug–phytochemical interactions Fexofenadine Intestinal Absorption - drug effects Intestinal Mucosa - metabolism Intestines - drug effects Male Original Research Article P-glycoprotein Permeability - drug effects Pharmacokinetics Pharmacotherapy Pharmacy Rats Rats, Wistar Resveratrol Stilbenes - pharmacology Terfenadine - analogs & derivatives Terfenadine - pharmacokinetics Verapamil - pharmacology |
| title | Effect of resveratrol on the pharmacokinetics of fexofenadine in rats: Involvement of P-glycoprotein inhibition |
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