Pharmacokinetic Basis for Using Saliva Matrine Concentrations as a Clinical Compliance Monitoring in Antitumor B Chemoprevention Trials in Humans
This study reports the first clinical evidence of significantly high secretion of matrine in a multi-component botanical (Antitumor B, ATB) into human saliva from the systemic circulation. This is of high clinical significance as matrine can be used as a monitoring tool during longitudinal clinical...
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| Veröffentlicht in: | Cancers 2022-12, Vol.15 (1), p.89 |
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| creator | Bui, Dinh McWilliams, Lenora A Wu, Lei Zhou, Haiying Wong, Stuart J You, Ming Chow, Diana S-L Singh, Rashim Hu, Ming |
| description | This study reports the first clinical evidence of significantly high secretion of matrine in a multi-component botanical (Antitumor B, ATB) into human saliva from the systemic circulation. This is of high clinical significance as matrine can be used as a monitoring tool during longitudinal clinical studies to overcome the key limitation of poor patient compliance often reported in cancer chemoprevention trials. Both matrine and dictamine were detected in the saliva and plasma samples but only matrine was quantifiable after the oral administration of ATB tablets (2400 mg) in 8 healthy volunteers. A significantly high saliva/plasma ratios for C
(6.5 ± 2.0) and AUC
(4.8 ± 2.0) of matrine suggested an active secretion in saliva probably due to entero-salivary recycling as evident from the long half-lives (t
plasma = 10.0 ± 2.8 h, t
saliva = 13.4 ± 6.9 h). The correlation between saliva and plasma levels of matrine was established using a population compartmental pharmacokinetic co-model. Moreover, a species-relevant PBPK model was developed to adequately describe the pharmacokinetic profiles of matrine in mouse, rat, and human. In conclusion, matrine saliva concentrations can be used as an excellent marker compound for mechanistic studies of active secretion of drugs from plasma to saliva as well as monitor the patient's compliance to the treatment regimen in upcoming clinical trials of ATB. |
| doi_str_mv | 10.3390/cancers15010089 |
| format | Article |
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(6.5 ± 2.0) and AUC
(4.8 ± 2.0) of matrine suggested an active secretion in saliva probably due to entero-salivary recycling as evident from the long half-lives (t
plasma = 10.0 ± 2.8 h, t
saliva = 13.4 ± 6.9 h). The correlation between saliva and plasma levels of matrine was established using a population compartmental pharmacokinetic co-model. Moreover, a species-relevant PBPK model was developed to adequately describe the pharmacokinetic profiles of matrine in mouse, rat, and human. In conclusion, matrine saliva concentrations can be used as an excellent marker compound for mechanistic studies of active secretion of drugs from plasma to saliva as well as monitor the patient's compliance to the treatment regimen in upcoming clinical trials of ATB.</description><identifier>ISSN: 2072-6694</identifier><identifier>EISSN: 2072-6694</identifier><identifier>DOI: 10.3390/cancers15010089</identifier><identifier>PMID: 36612086</identifier><language>eng</language><publisher>Switzerland: MDPI AG</publisher><subject>Alkaloids ; Biochemistry ; Chemoprevention ; Clinical trials ; Drug dosages ; Health aspects ; Methods ; Oral administration ; Oral cancer ; Patient compliance ; Patient monitoring ; Patients ; Pharmacokinetics ; Plant extracts ; Plasma ; Plasma levels ; Saliva ; Salivary diagnostics ; Secretion ; Software</subject><ispartof>Cancers, 2022-12, Vol.15 (1), p.89</ispartof><rights>COPYRIGHT 2022 MDPI AG</rights><rights>2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2022 by the authors. 2022</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c442t-744df3003ded30a252fa1e517e6099321d6d5af5ebe1cb7f04cf632f2c0089483</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/PMC9817974/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC9817974/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,885,27924,27925,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/36612086$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Bui, Dinh</creatorcontrib><creatorcontrib>McWilliams, Lenora A</creatorcontrib><creatorcontrib>Wu, Lei</creatorcontrib><creatorcontrib>Zhou, Haiying</creatorcontrib><creatorcontrib>Wong, Stuart J</creatorcontrib><creatorcontrib>You, Ming</creatorcontrib><creatorcontrib>Chow, Diana S-L</creatorcontrib><creatorcontrib>Singh, Rashim</creatorcontrib><creatorcontrib>Hu, Ming</creatorcontrib><title>Pharmacokinetic Basis for Using Saliva Matrine Concentrations as a Clinical Compliance Monitoring in Antitumor B Chemoprevention Trials in Humans</title><title>Cancers</title><addtitle>Cancers (Basel)</addtitle><description>This study reports the first clinical evidence of significantly high secretion of matrine in a multi-component botanical (Antitumor B, ATB) into human saliva from the systemic circulation. This is of high clinical significance as matrine can be used as a monitoring tool during longitudinal clinical studies to overcome the key limitation of poor patient compliance often reported in cancer chemoprevention trials. Both matrine and dictamine were detected in the saliva and plasma samples but only matrine was quantifiable after the oral administration of ATB tablets (2400 mg) in 8 healthy volunteers. A significantly high saliva/plasma ratios for C
(6.5 ± 2.0) and AUC
(4.8 ± 2.0) of matrine suggested an active secretion in saliva probably due to entero-salivary recycling as evident from the long half-lives (t
plasma = 10.0 ± 2.8 h, t
saliva = 13.4 ± 6.9 h). The correlation between saliva and plasma levels of matrine was established using a population compartmental pharmacokinetic co-model. Moreover, a species-relevant PBPK model was developed to adequately describe the pharmacokinetic profiles of matrine in mouse, rat, and human. In conclusion, matrine saliva concentrations can be used as an excellent marker compound for mechanistic studies of active secretion of drugs from plasma to saliva as well as monitor the patient's compliance to the treatment regimen in upcoming clinical trials of ATB.</description><subject>Alkaloids</subject><subject>Biochemistry</subject><subject>Chemoprevention</subject><subject>Clinical trials</subject><subject>Drug dosages</subject><subject>Health aspects</subject><subject>Methods</subject><subject>Oral administration</subject><subject>Oral cancer</subject><subject>Patient compliance</subject><subject>Patient monitoring</subject><subject>Patients</subject><subject>Pharmacokinetics</subject><subject>Plant extracts</subject><subject>Plasma</subject><subject>Plasma levels</subject><subject>Saliva</subject><subject>Salivary diagnostics</subject><subject>Secretion</subject><subject>Software</subject><issn>2072-6694</issn><issn>2072-6694</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</creationdate><recordtype>article</recordtype><sourceid>8G5</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNptkt9rFDEQxxdRbKl99k0CvvhybX5tsnkRrou2QouC7XPIZZO7qbvJmewe-Gf4Hzfr1doWk0DCzGe-kxmmqt4SfMKYwqfWBOtSJjUmGDfqRXVIsaQLIRR_-eh9UB3nfIvLYoxIIV9XB0wIQnEjDqvf3zYmDcbGHxDcCBadmQwZ-ZjQTYawRt9NDzuDrsyYCoHaWHKGMZkRYsjIlIPaHgJY0xfnsO1h_hW6igHGmGYFCGgZRhinoYieoXbjhrhNbldkiga6TmD6PFMX02BCflO98sXgju_vo-rm86fr9mJx-fX8S7u8XFjO6biQnHeelZo61zFsaE29Ia4m0gmsFKOkE11tfO1WjtiV9JhbLxj11M694g07qj7udbfTanDdvqpebxMMJv3S0YB-6gmw0eu406ohUkleBD7cC6T4c3J51ANk6_reBBenrKkUREnJhSro-2fobZxSKOX9obBqmob_o9amdxqCjyWvnUX1UvKaSkaVLNTJf6iyOzeAjcF5KPYnAaf7AJtizsn5hxoJ1vMg6WeDVCLePW7NA_93bNgdpKPGcg</recordid><startdate>20221223</startdate><enddate>20221223</enddate><creator>Bui, Dinh</creator><creator>McWilliams, Lenora A</creator><creator>Wu, Lei</creator><creator>Zhou, Haiying</creator><creator>Wong, Stuart J</creator><creator>You, Ming</creator><creator>Chow, Diana S-L</creator><creator>Singh, Rashim</creator><creator>Hu, Ming</creator><general>MDPI AG</general><general>MDPI</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7T5</scope><scope>7TO</scope><scope>7XB</scope><scope>8FE</scope><scope>8FH</scope><scope>8FK</scope><scope>8G5</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>H94</scope><scope>HCIFZ</scope><scope>LK8</scope><scope>M2O</scope><scope>M7P</scope><scope>MBDVC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20221223</creationdate><title>Pharmacokinetic Basis for Using Saliva Matrine Concentrations as a Clinical Compliance Monitoring in Antitumor B Chemoprevention Trials in Humans</title><author>Bui, Dinh ; McWilliams, Lenora A ; Wu, Lei ; Zhou, Haiying ; Wong, Stuart J ; You, Ming ; Chow, Diana S-L ; Singh, Rashim ; Hu, Ming</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c442t-744df3003ded30a252fa1e517e6099321d6d5af5ebe1cb7f04cf632f2c0089483</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2022</creationdate><topic>Alkaloids</topic><topic>Biochemistry</topic><topic>Chemoprevention</topic><topic>Clinical trials</topic><topic>Drug dosages</topic><topic>Health aspects</topic><topic>Methods</topic><topic>Oral administration</topic><topic>Oral cancer</topic><topic>Patient compliance</topic><topic>Patient monitoring</topic><topic>Patients</topic><topic>Pharmacokinetics</topic><topic>Plant extracts</topic><topic>Plasma</topic><topic>Plasma levels</topic><topic>Saliva</topic><topic>Salivary diagnostics</topic><topic>Secretion</topic><topic>Software</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Bui, Dinh</creatorcontrib><creatorcontrib>McWilliams, Lenora A</creatorcontrib><creatorcontrib>Wu, Lei</creatorcontrib><creatorcontrib>Zhou, Haiying</creatorcontrib><creatorcontrib>Wong, Stuart J</creatorcontrib><creatorcontrib>You, Ming</creatorcontrib><creatorcontrib>Chow, Diana S-L</creatorcontrib><creatorcontrib>Singh, Rashim</creatorcontrib><creatorcontrib>Hu, Ming</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Immunology Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Research Library (Alumni Edition)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>ProQuest Central Student</collection><collection>Research Library Prep</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Biological Science Collection</collection><collection>Research Library</collection><collection>Biological Science Database</collection><collection>Research Library (Corporate)</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>ProQuest Central Basic</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Cancers</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Bui, Dinh</au><au>McWilliams, Lenora A</au><au>Wu, Lei</au><au>Zhou, Haiying</au><au>Wong, Stuart J</au><au>You, Ming</au><au>Chow, Diana S-L</au><au>Singh, Rashim</au><au>Hu, Ming</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Pharmacokinetic Basis for Using Saliva Matrine Concentrations as a Clinical Compliance Monitoring in Antitumor B Chemoprevention Trials in Humans</atitle><jtitle>Cancers</jtitle><addtitle>Cancers (Basel)</addtitle><date>2022-12-23</date><risdate>2022</risdate><volume>15</volume><issue>1</issue><spage>89</spage><pages>89-</pages><issn>2072-6694</issn><eissn>2072-6694</eissn><abstract>This study reports the first clinical evidence of significantly high secretion of matrine in a multi-component botanical (Antitumor B, ATB) into human saliva from the systemic circulation. This is of high clinical significance as matrine can be used as a monitoring tool during longitudinal clinical studies to overcome the key limitation of poor patient compliance often reported in cancer chemoprevention trials. Both matrine and dictamine were detected in the saliva and plasma samples but only matrine was quantifiable after the oral administration of ATB tablets (2400 mg) in 8 healthy volunteers. A significantly high saliva/plasma ratios for C
(6.5 ± 2.0) and AUC
(4.8 ± 2.0) of matrine suggested an active secretion in saliva probably due to entero-salivary recycling as evident from the long half-lives (t
plasma = 10.0 ± 2.8 h, t
saliva = 13.4 ± 6.9 h). The correlation between saliva and plasma levels of matrine was established using a population compartmental pharmacokinetic co-model. Moreover, a species-relevant PBPK model was developed to adequately describe the pharmacokinetic profiles of matrine in mouse, rat, and human. In conclusion, matrine saliva concentrations can be used as an excellent marker compound for mechanistic studies of active secretion of drugs from plasma to saliva as well as monitor the patient's compliance to the treatment regimen in upcoming clinical trials of ATB.</abstract><cop>Switzerland</cop><pub>MDPI AG</pub><pmid>36612086</pmid><doi>10.3390/cancers15010089</doi><oa>free_for_read</oa></addata></record> |
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| subjects | Alkaloids Biochemistry Chemoprevention Clinical trials Drug dosages Health aspects Methods Oral administration Oral cancer Patient compliance Patient monitoring Patients Pharmacokinetics Plant extracts Plasma Plasma levels Saliva Salivary diagnostics Secretion Software |
| title | Pharmacokinetic Basis for Using Saliva Matrine Concentrations as a Clinical Compliance Monitoring in Antitumor B Chemoprevention Trials in Humans |
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