Population Pharmacokinetics of Sulindac and Genetic Polymorphisms of FMO3 and AOX1 in Women with Preterm Labor
Purpose This prospective study aimed to evaluate the effects of genetic polymorphisms in sulindac-related metabolizing enzyme genes including FMO3 and AOX1 on the population pharmacokinetics of sulindac in 58 pregnant women with preterm labor. Methods Plasma samples were collected at 1.5, 4, and 10 ...
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| Veröffentlicht in: | Pharmaceutical research 2020-03, Vol.37 (3), p.44-44, Article 44 |
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| creator | Sung, Jin Won Yun, Hwi-yeol Park, Sunny Kim, Young Ju Yee, Jeong Lee, Kyung Eun Song, Byungjeong Chung, Jee Eun Gwak, Hye Sun |
| description | Purpose
This prospective study aimed to evaluate the effects of genetic polymorphisms in sulindac-related metabolizing enzyme genes including FMO3 and AOX1 on the population pharmacokinetics of sulindac in 58 pregnant women with preterm labor.
Methods
Plasma samples were collected at 1.5, 4, and 10 h after first oral administration of sulindac. Plasma concentrations of sulindac and its active metabolite (sulindac sulfide) were determined, and pharmacokinetic analysis was performed with NONMEM 7.3.
Results
The mean maternal and gestational ages at the time of dosing were 32.5 ± 4.4 (range, 20–41) years and 27.4 ± 4.4 (range, 16.4–33.4) weeks, respectively. In the population pharmacokinetic analysis, one depot compartment model of sulindac with absorption lag time best described the data. The metabolism of sulindac and sulindac sulfide was described using Michaelis-Menten kinetics. In stepwise modeling, gestational age impacted volume of distribution (Vc), and FMO3 rs2266782 was shown by the Michaelis constant to affect conversion of sulindac sulfide to sulindac (K
M32
); these were retained in the final model.
Conclusions
Genetic polymorphisms of FMO3 and AOX1 could affect the pharmacokinetics of sulindac in women who undergo preterm labor. The results of this study could help clinicians develop individualized treatment plans for administering sulindac. |
| doi_str_mv | 10.1007/s11095-020-2765-6 |
| format | Article |
| fullrecord | <record><control><sourceid>gale_proqu</sourceid><recordid>TN_cdi_proquest_miscellaneous_2348230906</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><galeid>A747439153</galeid><sourcerecordid>A747439153</sourcerecordid><originalsourceid>FETCH-LOGICAL-c411t-3d0e5204428d809a58b48657d3d6cf7e70679aea88b3a5b97dca3f0278a3964e3</originalsourceid><addsrcrecordid>eNp9kVGL1DAQx4Mo3nr6AXyRgC--9Jw0aZM8LsfdKazsgor3FtJ0epuzTdakRe7b292egiAyD4GZ338Y8iPkNYMLBiDfZ8ZAVwWUUJSyror6CVmxSvJCg7h9SlYgS1EoKdgZeZHzPQAopsVzcsaZ1lzWsCJhFw9Tb0cfA93tbRqsi999wNG7TGNHP0-9D6111IaW3uBpQHexfxhiOux9Hk7U9actPxHr7S2jPtBvccBAf_pxT3cJR0wD3dgmppfkWWf7jK8e33Py9frqy-WHYrO9-Xi53hROMDYWvAWsShCiVK0CbSvVCFVXsuVt7TqJEmqpLVqlGm6rRsvWWd5BKZXluhbIz8m7Ze8hxR8T5tEMPjvsexswTtmUXKiSg4Z6Rt8u6J3t0fjQxTFZd8TNWgopuGYVn6mLf1BztTh4FwN2fu7_FWBLwKWYc8LOHJIfbHowDMzRnlnsmdmeOdozx1PePF49NQO2fxK_dc1AuQB5HoU7TOY-TinMP_mfrb8A8dSi1Q</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2348230906</pqid></control><display><type>article</type><title>Population Pharmacokinetics of Sulindac and Genetic Polymorphisms of FMO3 and AOX1 in Women with Preterm Labor</title><source>MEDLINE</source><source>SpringerLink Journals - AutoHoldings</source><creator>Sung, Jin Won ; Yun, Hwi-yeol ; Park, Sunny ; Kim, Young Ju ; Yee, Jeong ; Lee, Kyung Eun ; Song, Byungjeong ; Chung, Jee Eun ; Gwak, Hye Sun</creator><creatorcontrib>Sung, Jin Won ; Yun, Hwi-yeol ; Park, Sunny ; Kim, Young Ju ; Yee, Jeong ; Lee, Kyung Eun ; Song, Byungjeong ; Chung, Jee Eun ; Gwak, Hye Sun</creatorcontrib><description>Purpose
This prospective study aimed to evaluate the effects of genetic polymorphisms in sulindac-related metabolizing enzyme genes including FMO3 and AOX1 on the population pharmacokinetics of sulindac in 58 pregnant women with preterm labor.
Methods
Plasma samples were collected at 1.5, 4, and 10 h after first oral administration of sulindac. Plasma concentrations of sulindac and its active metabolite (sulindac sulfide) were determined, and pharmacokinetic analysis was performed with NONMEM 7.3.
Results
The mean maternal and gestational ages at the time of dosing were 32.5 ± 4.4 (range, 20–41) years and 27.4 ± 4.4 (range, 16.4–33.4) weeks, respectively. In the population pharmacokinetic analysis, one depot compartment model of sulindac with absorption lag time best described the data. The metabolism of sulindac and sulindac sulfide was described using Michaelis-Menten kinetics. In stepwise modeling, gestational age impacted volume of distribution (Vc), and FMO3 rs2266782 was shown by the Michaelis constant to affect conversion of sulindac sulfide to sulindac (K
M32
); these were retained in the final model.
Conclusions
Genetic polymorphisms of FMO3 and AOX1 could affect the pharmacokinetics of sulindac in women who undergo preterm labor. The results of this study could help clinicians develop individualized treatment plans for administering sulindac.</description><identifier>ISSN: 0724-8741</identifier><identifier>EISSN: 1573-904X</identifier><identifier>DOI: 10.1007/s11095-020-2765-6</identifier><identifier>PMID: 31993760</identifier><language>eng</language><publisher>New York: Springer US</publisher><subject>Adult ; Aldehyde Oxidase - genetics ; Aldehyde Oxidase - metabolism ; Analysis ; Anti-Inflammatory Agents - pharmacokinetics ; Biochemistry ; Biomedical and Life Sciences ; Biomedical Engineering and Bioengineering ; Biomedicine ; Enzyme kinetics ; Enzymes ; Ethylenediaminetetraacetic acid ; Female ; Genetic aspects ; Genetic polymorphisms ; Genetic research ; Genotype ; Gestational Age ; Humans ; Medical Law ; Metabolites ; Models, Biological ; Obstetric Labor, Premature - metabolism ; Oxygenases - genetics ; Oxygenases - metabolism ; Pharmacology/Toxicology ; Pharmacy ; Polymorphism, Genetic - physiology ; Pregnancy ; Pregnant women ; Premature labor ; Prospective Studies ; Research Paper ; Signal Transduction ; Sulfides ; Sulindac ; Sulindac - analogs & derivatives ; Sulindac - metabolism ; Sulindac - pharmacokinetics</subject><ispartof>Pharmaceutical research, 2020-03, Vol.37 (3), p.44-44, Article 44</ispartof><rights>Springer Science+Business Media, LLC, part of Springer Nature 2020</rights><rights>COPYRIGHT 2020 Springer</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c411t-3d0e5204428d809a58b48657d3d6cf7e70679aea88b3a5b97dca3f0278a3964e3</citedby><cites>FETCH-LOGICAL-c411t-3d0e5204428d809a58b48657d3d6cf7e70679aea88b3a5b97dca3f0278a3964e3</cites><orcidid>0000-0003-0278-2563</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/s11095-020-2765-6$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s11095-020-2765-6$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,776,780,27903,27904,41467,42536,51297</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/31993760$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Sung, Jin Won</creatorcontrib><creatorcontrib>Yun, Hwi-yeol</creatorcontrib><creatorcontrib>Park, Sunny</creatorcontrib><creatorcontrib>Kim, Young Ju</creatorcontrib><creatorcontrib>Yee, Jeong</creatorcontrib><creatorcontrib>Lee, Kyung Eun</creatorcontrib><creatorcontrib>Song, Byungjeong</creatorcontrib><creatorcontrib>Chung, Jee Eun</creatorcontrib><creatorcontrib>Gwak, Hye Sun</creatorcontrib><title>Population Pharmacokinetics of Sulindac and Genetic Polymorphisms of FMO3 and AOX1 in Women with Preterm Labor</title><title>Pharmaceutical research</title><addtitle>Pharm Res</addtitle><addtitle>Pharm Res</addtitle><description>Purpose
This prospective study aimed to evaluate the effects of genetic polymorphisms in sulindac-related metabolizing enzyme genes including FMO3 and AOX1 on the population pharmacokinetics of sulindac in 58 pregnant women with preterm labor.
Methods
Plasma samples were collected at 1.5, 4, and 10 h after first oral administration of sulindac. Plasma concentrations of sulindac and its active metabolite (sulindac sulfide) were determined, and pharmacokinetic analysis was performed with NONMEM 7.3.
Results
The mean maternal and gestational ages at the time of dosing were 32.5 ± 4.4 (range, 20–41) years and 27.4 ± 4.4 (range, 16.4–33.4) weeks, respectively. In the population pharmacokinetic analysis, one depot compartment model of sulindac with absorption lag time best described the data. The metabolism of sulindac and sulindac sulfide was described using Michaelis-Menten kinetics. In stepwise modeling, gestational age impacted volume of distribution (Vc), and FMO3 rs2266782 was shown by the Michaelis constant to affect conversion of sulindac sulfide to sulindac (K
M32
); these were retained in the final model.
Conclusions
Genetic polymorphisms of FMO3 and AOX1 could affect the pharmacokinetics of sulindac in women who undergo preterm labor. The results of this study could help clinicians develop individualized treatment plans for administering sulindac.</description><subject>Adult</subject><subject>Aldehyde Oxidase - genetics</subject><subject>Aldehyde Oxidase - metabolism</subject><subject>Analysis</subject><subject>Anti-Inflammatory Agents - pharmacokinetics</subject><subject>Biochemistry</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedical Engineering and Bioengineering</subject><subject>Biomedicine</subject><subject>Enzyme kinetics</subject><subject>Enzymes</subject><subject>Ethylenediaminetetraacetic acid</subject><subject>Female</subject><subject>Genetic aspects</subject><subject>Genetic polymorphisms</subject><subject>Genetic research</subject><subject>Genotype</subject><subject>Gestational Age</subject><subject>Humans</subject><subject>Medical Law</subject><subject>Metabolites</subject><subject>Models, Biological</subject><subject>Obstetric Labor, Premature - metabolism</subject><subject>Oxygenases - genetics</subject><subject>Oxygenases - metabolism</subject><subject>Pharmacology/Toxicology</subject><subject>Pharmacy</subject><subject>Polymorphism, Genetic - physiology</subject><subject>Pregnancy</subject><subject>Pregnant women</subject><subject>Premature labor</subject><subject>Prospective Studies</subject><subject>Research Paper</subject><subject>Signal Transduction</subject><subject>Sulfides</subject><subject>Sulindac</subject><subject>Sulindac - analogs & derivatives</subject><subject>Sulindac - metabolism</subject><subject>Sulindac - pharmacokinetics</subject><issn>0724-8741</issn><issn>1573-904X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kVGL1DAQx4Mo3nr6AXyRgC--9Jw0aZM8LsfdKazsgor3FtJ0epuzTdakRe7b292egiAyD4GZ338Y8iPkNYMLBiDfZ8ZAVwWUUJSyror6CVmxSvJCg7h9SlYgS1EoKdgZeZHzPQAopsVzcsaZ1lzWsCJhFw9Tb0cfA93tbRqsi999wNG7TGNHP0-9D6111IaW3uBpQHexfxhiOux9Hk7U9actPxHr7S2jPtBvccBAf_pxT3cJR0wD3dgmppfkWWf7jK8e33Py9frqy-WHYrO9-Xi53hROMDYWvAWsShCiVK0CbSvVCFVXsuVt7TqJEmqpLVqlGm6rRsvWWd5BKZXluhbIz8m7Ze8hxR8T5tEMPjvsexswTtmUXKiSg4Z6Rt8u6J3t0fjQxTFZd8TNWgopuGYVn6mLf1BztTh4FwN2fu7_FWBLwKWYc8LOHJIfbHowDMzRnlnsmdmeOdozx1PePF49NQO2fxK_dc1AuQB5HoU7TOY-TinMP_mfrb8A8dSi1Q</recordid><startdate>20200301</startdate><enddate>20200301</enddate><creator>Sung, Jin Won</creator><creator>Yun, Hwi-yeol</creator><creator>Park, Sunny</creator><creator>Kim, Young Ju</creator><creator>Yee, Jeong</creator><creator>Lee, Kyung Eun</creator><creator>Song, Byungjeong</creator><creator>Chung, Jee Eun</creator><creator>Gwak, Hye Sun</creator><general>Springer US</general><general>Springer</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><orcidid>https://orcid.org/0000-0003-0278-2563</orcidid></search><sort><creationdate>20200301</creationdate><title>Population Pharmacokinetics of Sulindac and Genetic Polymorphisms of FMO3 and AOX1 in Women with Preterm Labor</title><author>Sung, Jin Won ; Yun, Hwi-yeol ; Park, Sunny ; Kim, Young Ju ; Yee, Jeong ; Lee, Kyung Eun ; Song, Byungjeong ; Chung, Jee Eun ; Gwak, Hye Sun</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c411t-3d0e5204428d809a58b48657d3d6cf7e70679aea88b3a5b97dca3f0278a3964e3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Adult</topic><topic>Aldehyde Oxidase - genetics</topic><topic>Aldehyde Oxidase - metabolism</topic><topic>Analysis</topic><topic>Anti-Inflammatory Agents - pharmacokinetics</topic><topic>Biochemistry</topic><topic>Biomedical and Life Sciences</topic><topic>Biomedical Engineering and Bioengineering</topic><topic>Biomedicine</topic><topic>Enzyme kinetics</topic><topic>Enzymes</topic><topic>Ethylenediaminetetraacetic acid</topic><topic>Female</topic><topic>Genetic aspects</topic><topic>Genetic polymorphisms</topic><topic>Genetic research</topic><topic>Genotype</topic><topic>Gestational Age</topic><topic>Humans</topic><topic>Medical Law</topic><topic>Metabolites</topic><topic>Models, Biological</topic><topic>Obstetric Labor, Premature - metabolism</topic><topic>Oxygenases - genetics</topic><topic>Oxygenases - metabolism</topic><topic>Pharmacology/Toxicology</topic><topic>Pharmacy</topic><topic>Polymorphism, Genetic - physiology</topic><topic>Pregnancy</topic><topic>Pregnant women</topic><topic>Premature labor</topic><topic>Prospective Studies</topic><topic>Research Paper</topic><topic>Signal Transduction</topic><topic>Sulfides</topic><topic>Sulindac</topic><topic>Sulindac - analogs & derivatives</topic><topic>Sulindac - metabolism</topic><topic>Sulindac - pharmacokinetics</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Sung, Jin Won</creatorcontrib><creatorcontrib>Yun, Hwi-yeol</creatorcontrib><creatorcontrib>Park, Sunny</creatorcontrib><creatorcontrib>Kim, Young Ju</creatorcontrib><creatorcontrib>Yee, Jeong</creatorcontrib><creatorcontrib>Lee, Kyung Eun</creatorcontrib><creatorcontrib>Song, Byungjeong</creatorcontrib><creatorcontrib>Chung, Jee Eun</creatorcontrib><creatorcontrib>Gwak, Hye Sun</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>Pharmaceutical research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Sung, Jin Won</au><au>Yun, Hwi-yeol</au><au>Park, Sunny</au><au>Kim, Young Ju</au><au>Yee, Jeong</au><au>Lee, Kyung Eun</au><au>Song, Byungjeong</au><au>Chung, Jee Eun</au><au>Gwak, Hye Sun</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Population Pharmacokinetics of Sulindac and Genetic Polymorphisms of FMO3 and AOX1 in Women with Preterm Labor</atitle><jtitle>Pharmaceutical research</jtitle><stitle>Pharm Res</stitle><addtitle>Pharm Res</addtitle><date>2020-03-01</date><risdate>2020</risdate><volume>37</volume><issue>3</issue><spage>44</spage><epage>44</epage><pages>44-44</pages><artnum>44</artnum><issn>0724-8741</issn><eissn>1573-904X</eissn><abstract>Purpose
This prospective study aimed to evaluate the effects of genetic polymorphisms in sulindac-related metabolizing enzyme genes including FMO3 and AOX1 on the population pharmacokinetics of sulindac in 58 pregnant women with preterm labor.
Methods
Plasma samples were collected at 1.5, 4, and 10 h after first oral administration of sulindac. Plasma concentrations of sulindac and its active metabolite (sulindac sulfide) were determined, and pharmacokinetic analysis was performed with NONMEM 7.3.
Results
The mean maternal and gestational ages at the time of dosing were 32.5 ± 4.4 (range, 20–41) years and 27.4 ± 4.4 (range, 16.4–33.4) weeks, respectively. In the population pharmacokinetic analysis, one depot compartment model of sulindac with absorption lag time best described the data. The metabolism of sulindac and sulindac sulfide was described using Michaelis-Menten kinetics. In stepwise modeling, gestational age impacted volume of distribution (Vc), and FMO3 rs2266782 was shown by the Michaelis constant to affect conversion of sulindac sulfide to sulindac (K
M32
); these were retained in the final model.
Conclusions
Genetic polymorphisms of FMO3 and AOX1 could affect the pharmacokinetics of sulindac in women who undergo preterm labor. The results of this study could help clinicians develop individualized treatment plans for administering sulindac.</abstract><cop>New York</cop><pub>Springer US</pub><pmid>31993760</pmid><doi>10.1007/s11095-020-2765-6</doi><tpages>1</tpages><orcidid>https://orcid.org/0000-0003-0278-2563</orcidid></addata></record> |
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| subjects | Adult Aldehyde Oxidase - genetics Aldehyde Oxidase - metabolism Analysis Anti-Inflammatory Agents - pharmacokinetics Biochemistry Biomedical and Life Sciences Biomedical Engineering and Bioengineering Biomedicine Enzyme kinetics Enzymes Ethylenediaminetetraacetic acid Female Genetic aspects Genetic polymorphisms Genetic research Genotype Gestational Age Humans Medical Law Metabolites Models, Biological Obstetric Labor, Premature - metabolism Oxygenases - genetics Oxygenases - metabolism Pharmacology/Toxicology Pharmacy Polymorphism, Genetic - physiology Pregnancy Pregnant women Premature labor Prospective Studies Research Paper Signal Transduction Sulfides Sulindac Sulindac - analogs & derivatives Sulindac - metabolism Sulindac - pharmacokinetics |
| title | Population Pharmacokinetics of Sulindac and Genetic Polymorphisms of FMO3 and AOX1 in Women with Preterm Labor |
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