Influence of verapamil on the pharmacokinetics of oridonin in rats
Context: Oridonin has been traditionally used in Chinese treatment of various cancers, but its poor bioavailability limits its therapeutic uses. Verapamil can enhance the absorption of some drugs with poor oral bioavailability. Whether verapamil can enhance the bioavailability of oridonin is still u...
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| Veröffentlicht in: | Pharmaceutical biology 2019-01, Vol.57 (1), p.787-791 |
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| creator | Liu, Jing Zhang, Ning Li, Na Fan, Xiaocheng Li, Ying |
| description | Context: Oridonin has been traditionally used in Chinese treatment of various cancers, but its poor bioavailability limits its therapeutic uses. Verapamil can enhance the absorption of some drugs with poor oral bioavailability. Whether verapamil can enhance the bioavailability of oridonin is still unclear.
Objective: This study investigated the effect of verapamil on the pharmacokinetics of oridonin in rats and clarified its main mechanism.
Materials and methods: The pharmacokinetic profiles of oral administration of oridonin (20 mg/kg) in Sprague-Dawley rats with two groups of six animals each, with or without pre-treatment of verapamil (10 mg/kg/day for 7 days) were investigated. The effects of verapamil on the transport and metabolic stability of oridonin were also investigated using Caco-2 cell transwell model and rat liver microsomes.
Results: The results showed that verapamil could significantly increase the peak plasma concentration (from 146.9 ± 10.17 to 193.97 ± 10.53 ng/mL), and decrease the oral clearance (from 14.69 ± 4.42 to 8.09 ± 3.03 L/h/kg) of oridonin. The Caco-2 cell transwell experiments indicated that verapamil could decrease the efflux ratio of oridonin from 1.67 to 1.15, and the intrinsic clearance rate of oridonin was decreased by the pre-treatment with verapamil (40.06 ± 2.5 vs. 36.09 ± 3.7 µL/min/mg protein).
Discussion and conclusions: These results indicated that verapamil could significantly change the pharmacokinetic profile of oridonin in rats, and it might exert these effects through increasing the absorption of oridonin by inhibiting the activity of P-gp, or through inhibiting the metabolism of oridonin in rat liver. In addition, the potential drug-drug interaction should be given special attention when verapamil is used with oridonin. Also, the dose of oridonin should be carefully selected in the clinic. |
| doi_str_mv | 10.1080/13880209.2019.1688844 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_6882484</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><doaj_id>oai_doaj_org_article_4e27aaa791904179aeb0edeac67b4784</doaj_id><sourcerecordid>2391268803</sourcerecordid><originalsourceid>FETCH-LOGICAL-c562t-8022e8db5749716633366014a6de26184ddb95f317548da4a77e27e8f9b798c73</originalsourceid><addsrcrecordid>eNp9kVtv1DAQhSMEoqXwE0CReM7iW3x5QUDFZaVKvMCzNbGdrpesvdjZov57Jt1tRV-QLNmyvzlzxqdpXlOyokSTd5RrTRgxK0aoWVGptRbiSXNOlRBdT6l8imdkugU6a17UuiWE9Jz3z5szjpRC_rz5tE7jdAjJhTaP7U0osIddnNqc2nkT2v0Gyg5c_hVTmKOrC5RL9DnF1OIqMNeXzbMRphpenfaL5ueXzz8uv3VX37-uLz9eda6XbO7QLQvaD70SRlEpOedSEipA-sAk1cL7wfQjWuuF9iBAqcBU0KMZlNFO8YtmfdT1GbZ2X-IOyq3NEO3dRS7XFgqanIIVWAkAylBDBFUGwkCCD-CkGpbBUev9UWt_GHbBu5DmAtMj0ccvKW7sdb6x-M9M3Am8PQmU_PsQ6my3-VASzm8ZN5QhRzhS_ZFyJddawvjQgRK7xGjvY7RLjPYUI9a9-dfeQ9V9bgh8OAIxjRkT-pPL5O0Mt1MuY4HkYkX4vz3-Ashkq5U</addsrcrecordid><sourcetype>Open Website</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2391268803</pqid></control><display><type>article</type><title>Influence of verapamil on the pharmacokinetics of oridonin in rats</title><source>MEDLINE</source><source>DOAJ Directory of Open Access Journals</source><source>Access via Taylor & Francis (Open Access Collection)</source><source>PubMed Central</source><source>Alma/SFX Local Collection</source><creator>Liu, Jing ; Zhang, Ning ; Li, Na ; Fan, Xiaocheng ; Li, Ying</creator><creatorcontrib>Liu, Jing ; Zhang, Ning ; Li, Na ; Fan, Xiaocheng ; Li, Ying</creatorcontrib><description>Context: Oridonin has been traditionally used in Chinese treatment of various cancers, but its poor bioavailability limits its therapeutic uses. Verapamil can enhance the absorption of some drugs with poor oral bioavailability. Whether verapamil can enhance the bioavailability of oridonin is still unclear.
Objective: This study investigated the effect of verapamil on the pharmacokinetics of oridonin in rats and clarified its main mechanism.
Materials and methods: The pharmacokinetic profiles of oral administration of oridonin (20 mg/kg) in Sprague-Dawley rats with two groups of six animals each, with or without pre-treatment of verapamil (10 mg/kg/day for 7 days) were investigated. The effects of verapamil on the transport and metabolic stability of oridonin were also investigated using Caco-2 cell transwell model and rat liver microsomes.
Results: The results showed that verapamil could significantly increase the peak plasma concentration (from 146.9 ± 10.17 to 193.97 ± 10.53 ng/mL), and decrease the oral clearance (from 14.69 ± 4.42 to 8.09 ± 3.03 L/h/kg) of oridonin. The Caco-2 cell transwell experiments indicated that verapamil could decrease the efflux ratio of oridonin from 1.67 to 1.15, and the intrinsic clearance rate of oridonin was decreased by the pre-treatment with verapamil (40.06 ± 2.5 vs. 36.09 ± 3.7 µL/min/mg protein).
Discussion and conclusions: These results indicated that verapamil could significantly change the pharmacokinetic profile of oridonin in rats, and it might exert these effects through increasing the absorption of oridonin by inhibiting the activity of P-gp, or through inhibiting the metabolism of oridonin in rat liver. In addition, the potential drug-drug interaction should be given special attention when verapamil is used with oridonin. Also, the dose of oridonin should be carefully selected in the clinic.</description><identifier>ISSN: 1388-0209</identifier><identifier>EISSN: 1744-5116</identifier><identifier>DOI: 10.1080/13880209.2019.1688844</identifier><identifier>PMID: 31747844</identifier><language>eng</language><publisher>England: Taylor & Francis</publisher><subject>Administration, Oral ; Animals ; Bioavailability ; Biological Availability ; Caco-2 Cells ; Cancer ; Chinese medicine ; CYP3A4 ; Diterpenes, Kaurane - metabolism ; Diterpenes, Kaurane - pharmacokinetics ; Drug dosages ; Drug interaction ; Drug Interactions ; drug-drug interaction ; Experiments ; Humans ; Liver ; Metabolic Clearance Rate - drug effects ; Microsomes ; Microsomes, Liver - drug effects ; Oral administration ; P-gp ; Pharmacokinetics ; Plasma ; Rats ; Rats, Sprague-Dawley ; Rodents ; Verapamil ; Verapamil - blood ; Verapamil - pharmacology</subject><ispartof>Pharmaceutical biology, 2019-01, Vol.57 (1), p.787-791</ispartof><rights>2019 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. 2019</rights><rights>2019 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. This work is licensed under the Creative Commons Attribution License http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2019 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. 2019 The Author(s)</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c562t-8022e8db5749716633366014a6de26184ddb95f317548da4a77e27e8f9b798c73</citedby><cites>FETCH-LOGICAL-c562t-8022e8db5749716633366014a6de26184ddb95f317548da4a77e27e8f9b798c73</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6882484/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6882484/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,2102,27502,27924,27925,53791,53793,59143,59144</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/31747844$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Liu, Jing</creatorcontrib><creatorcontrib>Zhang, Ning</creatorcontrib><creatorcontrib>Li, Na</creatorcontrib><creatorcontrib>Fan, Xiaocheng</creatorcontrib><creatorcontrib>Li, Ying</creatorcontrib><title>Influence of verapamil on the pharmacokinetics of oridonin in rats</title><title>Pharmaceutical biology</title><addtitle>Pharm Biol</addtitle><description>Context: Oridonin has been traditionally used in Chinese treatment of various cancers, but its poor bioavailability limits its therapeutic uses. Verapamil can enhance the absorption of some drugs with poor oral bioavailability. Whether verapamil can enhance the bioavailability of oridonin is still unclear.
Objective: This study investigated the effect of verapamil on the pharmacokinetics of oridonin in rats and clarified its main mechanism.
Materials and methods: The pharmacokinetic profiles of oral administration of oridonin (20 mg/kg) in Sprague-Dawley rats with two groups of six animals each, with or without pre-treatment of verapamil (10 mg/kg/day for 7 days) were investigated. The effects of verapamil on the transport and metabolic stability of oridonin were also investigated using Caco-2 cell transwell model and rat liver microsomes.
Results: The results showed that verapamil could significantly increase the peak plasma concentration (from 146.9 ± 10.17 to 193.97 ± 10.53 ng/mL), and decrease the oral clearance (from 14.69 ± 4.42 to 8.09 ± 3.03 L/h/kg) of oridonin. The Caco-2 cell transwell experiments indicated that verapamil could decrease the efflux ratio of oridonin from 1.67 to 1.15, and the intrinsic clearance rate of oridonin was decreased by the pre-treatment with verapamil (40.06 ± 2.5 vs. 36.09 ± 3.7 µL/min/mg protein).
Discussion and conclusions: These results indicated that verapamil could significantly change the pharmacokinetic profile of oridonin in rats, and it might exert these effects through increasing the absorption of oridonin by inhibiting the activity of P-gp, or through inhibiting the metabolism of oridonin in rat liver. In addition, the potential drug-drug interaction should be given special attention when verapamil is used with oridonin. Also, the dose of oridonin should be carefully selected in the clinic.</description><subject>Administration, Oral</subject><subject>Animals</subject><subject>Bioavailability</subject><subject>Biological Availability</subject><subject>Caco-2 Cells</subject><subject>Cancer</subject><subject>Chinese medicine</subject><subject>CYP3A4</subject><subject>Diterpenes, Kaurane - metabolism</subject><subject>Diterpenes, Kaurane - pharmacokinetics</subject><subject>Drug dosages</subject><subject>Drug interaction</subject><subject>Drug Interactions</subject><subject>drug-drug interaction</subject><subject>Experiments</subject><subject>Humans</subject><subject>Liver</subject><subject>Metabolic Clearance Rate - drug effects</subject><subject>Microsomes</subject><subject>Microsomes, Liver - drug effects</subject><subject>Oral administration</subject><subject>P-gp</subject><subject>Pharmacokinetics</subject><subject>Plasma</subject><subject>Rats</subject><subject>Rats, Sprague-Dawley</subject><subject>Rodents</subject><subject>Verapamil</subject><subject>Verapamil - blood</subject><subject>Verapamil - pharmacology</subject><issn>1388-0209</issn><issn>1744-5116</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><sourceid>0YH</sourceid><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>DOA</sourceid><recordid>eNp9kVtv1DAQhSMEoqXwE0CReM7iW3x5QUDFZaVKvMCzNbGdrpesvdjZov57Jt1tRV-QLNmyvzlzxqdpXlOyokSTd5RrTRgxK0aoWVGptRbiSXNOlRBdT6l8imdkugU6a17UuiWE9Jz3z5szjpRC_rz5tE7jdAjJhTaP7U0osIddnNqc2nkT2v0Gyg5c_hVTmKOrC5RL9DnF1OIqMNeXzbMRphpenfaL5ueXzz8uv3VX37-uLz9eda6XbO7QLQvaD70SRlEpOedSEipA-sAk1cL7wfQjWuuF9iBAqcBU0KMZlNFO8YtmfdT1GbZ2X-IOyq3NEO3dRS7XFgqanIIVWAkAylBDBFUGwkCCD-CkGpbBUev9UWt_GHbBu5DmAtMj0ccvKW7sdb6x-M9M3Am8PQmU_PsQ6my3-VASzm8ZN5QhRzhS_ZFyJddawvjQgRK7xGjvY7RLjPYUI9a9-dfeQ9V9bgh8OAIxjRkT-pPL5O0Mt1MuY4HkYkX4vz3-Ashkq5U</recordid><startdate>20190101</startdate><enddate>20190101</enddate><creator>Liu, Jing</creator><creator>Zhang, Ning</creator><creator>Li, Na</creator><creator>Fan, Xiaocheng</creator><creator>Li, Ying</creator><general>Taylor & Francis</general><general>Taylor & Francis Ltd</general><general>Taylor & Francis Group</general><scope>0YH</scope><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>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>8FD</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>K9.</scope><scope>M0S</scope><scope>P64</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>RC3</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20190101</creationdate><title>Influence of verapamil on the pharmacokinetics of oridonin in rats</title><author>Liu, Jing ; Zhang, Ning ; Li, Na ; Fan, Xiaocheng ; Li, Ying</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c562t-8022e8db5749716633366014a6de26184ddb95f317548da4a77e27e8f9b798c73</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>Administration, Oral</topic><topic>Animals</topic><topic>Bioavailability</topic><topic>Biological Availability</topic><topic>Caco-2 Cells</topic><topic>Cancer</topic><topic>Chinese medicine</topic><topic>CYP3A4</topic><topic>Diterpenes, Kaurane - metabolism</topic><topic>Diterpenes, Kaurane - pharmacokinetics</topic><topic>Drug dosages</topic><topic>Drug interaction</topic><topic>Drug Interactions</topic><topic>drug-drug interaction</topic><topic>Experiments</topic><topic>Humans</topic><topic>Liver</topic><topic>Metabolic Clearance Rate - drug effects</topic><topic>Microsomes</topic><topic>Microsomes, Liver - drug effects</topic><topic>Oral administration</topic><topic>P-gp</topic><topic>Pharmacokinetics</topic><topic>Plasma</topic><topic>Rats</topic><topic>Rats, Sprague-Dawley</topic><topic>Rodents</topic><topic>Verapamil</topic><topic>Verapamil - blood</topic><topic>Verapamil - pharmacology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Liu, Jing</creatorcontrib><creatorcontrib>Zhang, Ning</creatorcontrib><creatorcontrib>Li, Na</creatorcontrib><creatorcontrib>Fan, Xiaocheng</creatorcontrib><creatorcontrib>Li, Ying</creatorcontrib><collection>Access via Taylor & Francis (Open Access Collection)</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Technology Research Database</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 Essentials</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Publicly Available Content Database</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>Genetics Abstracts</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>Pharmaceutical biology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Liu, Jing</au><au>Zhang, Ning</au><au>Li, Na</au><au>Fan, Xiaocheng</au><au>Li, Ying</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Influence of verapamil on the pharmacokinetics of oridonin in rats</atitle><jtitle>Pharmaceutical biology</jtitle><addtitle>Pharm Biol</addtitle><date>2019-01-01</date><risdate>2019</risdate><volume>57</volume><issue>1</issue><spage>787</spage><epage>791</epage><pages>787-791</pages><issn>1388-0209</issn><eissn>1744-5116</eissn><abstract>Context: Oridonin has been traditionally used in Chinese treatment of various cancers, but its poor bioavailability limits its therapeutic uses. Verapamil can enhance the absorption of some drugs with poor oral bioavailability. Whether verapamil can enhance the bioavailability of oridonin is still unclear.
Objective: This study investigated the effect of verapamil on the pharmacokinetics of oridonin in rats and clarified its main mechanism.
Materials and methods: The pharmacokinetic profiles of oral administration of oridonin (20 mg/kg) in Sprague-Dawley rats with two groups of six animals each, with or without pre-treatment of verapamil (10 mg/kg/day for 7 days) were investigated. The effects of verapamil on the transport and metabolic stability of oridonin were also investigated using Caco-2 cell transwell model and rat liver microsomes.
Results: The results showed that verapamil could significantly increase the peak plasma concentration (from 146.9 ± 10.17 to 193.97 ± 10.53 ng/mL), and decrease the oral clearance (from 14.69 ± 4.42 to 8.09 ± 3.03 L/h/kg) of oridonin. The Caco-2 cell transwell experiments indicated that verapamil could decrease the efflux ratio of oridonin from 1.67 to 1.15, and the intrinsic clearance rate of oridonin was decreased by the pre-treatment with verapamil (40.06 ± 2.5 vs. 36.09 ± 3.7 µL/min/mg protein).
Discussion and conclusions: These results indicated that verapamil could significantly change the pharmacokinetic profile of oridonin in rats, and it might exert these effects through increasing the absorption of oridonin by inhibiting the activity of P-gp, or through inhibiting the metabolism of oridonin in rat liver. In addition, the potential drug-drug interaction should be given special attention when verapamil is used with oridonin. Also, the dose of oridonin should be carefully selected in the clinic.</abstract><cop>England</cop><pub>Taylor & Francis</pub><pmid>31747844</pmid><doi>10.1080/13880209.2019.1688844</doi><tpages>5</tpages><oa>free_for_read</oa></addata></record> |
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| source | MEDLINE; DOAJ Directory of Open Access Journals; Access via Taylor & Francis (Open Access Collection); PubMed Central; Alma/SFX Local Collection |
| subjects | Administration, Oral Animals Bioavailability Biological Availability Caco-2 Cells Cancer Chinese medicine CYP3A4 Diterpenes, Kaurane - metabolism Diterpenes, Kaurane - pharmacokinetics Drug dosages Drug interaction Drug Interactions drug-drug interaction Experiments Humans Liver Metabolic Clearance Rate - drug effects Microsomes Microsomes, Liver - drug effects Oral administration P-gp Pharmacokinetics Plasma Rats Rats, Sprague-Dawley Rodents Verapamil Verapamil - blood Verapamil - pharmacology |
| title | Influence of verapamil on the pharmacokinetics of oridonin in rats |
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