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Effects of CYP2C9 genetic polymorphisms on the pharmacokinetics of celecoxib and its carboxylic acid metabolite
Celecoxib, a selective cyclooxygenase (COX)-2 inhibitor, is used for the treatment of rheumatoid arthritis and osteoarthritis. The predominant hepatic metabolism of celecoxib to celecoxib carboxylic acid (CCA) is mediated mainly by CYP2C9. We investigated the effects of the major CYP2C9 genetic vari...
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| Published in: | Archives of pharmacal research 2017, 40(3), , pp.382-390 |
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| creator | Kim, Se-Hyung Kim, Do-Hoon Byeon, Ji-Yeong Kim, Young-Hoon Kim, Dong-Hyun Lim, Hye-Jin Lee, Choong-Min Whang, Sang Sup Choi, Chang-Ik Bae, Jung-Woo Lee, Yun Jeong Jang, Choon-Gon Lee, Seok-Yong |
| description | Celecoxib, a selective cyclooxygenase (COX)-2 inhibitor, is used for the treatment of rheumatoid arthritis and osteoarthritis. The predominant hepatic metabolism of celecoxib to celecoxib carboxylic acid (CCA) is mediated mainly by CYP2C9. We investigated the effects of the major
CYP2C9
genetic variants in Asian populations,
CYP2C9*3
and
CYP2C9*13
, on the pharmacokinetics of celecoxib and its carboxylic acid metabolite in healthy Korean subjects. A single 200-mg oral dose of celecoxib was given to 52 Korean subjects with different
CYP2C9
genotypes: CYP2C9EM (n = 26;
CYP2C9*1/*1
), CYP2C9IM (n = 24;
CYP2C9*1/*3
and
*1/*13
), and CYP2C9PM (n = 2;
CYP2C9*3/*3
). Celecoxib and CCA concentrations in plasma samples collected up to 48 or 96 h after drug intake were determined by HPLC–MS/MS. The mean area under the plasma concentration–time curve (AUC
0–∞
) of celecoxib was increased 1.63-fold (
P
|
| doi_str_mv | 10.1007/s12272-016-0861-2 |
| format | article |
| fullrecord | <record><control><sourceid>proquest_nrf_k</sourceid><recordid>TN_cdi_nrf_kci_oai_kci_go_kr_ARTI_1343956</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>1841798777</sourcerecordid><originalsourceid>FETCH-LOGICAL-c444t-9e40b0554b3991a93bab904db0e41dc84ec2a58f502e534b3a2134d8ebdd5eeb3</originalsourceid><addsrcrecordid>eNp9kU1P3DAURa2qVRmgP6Cbyku6CPV34iUa0RYJiaqiC1aW7bzMmEniYGck5t_XTCjLrt7innsk-yL0mZJLSkj9LVPGalYRqirSKFqxd2hFda0qXjfqPVoRJnmlmNIn6DTnR0K4klJ-RCes5EIpskLxuuvAzxnHDq8ffrG1xhsYYQ4eT7E_DDFN25CHko943gKetjYN1sddOELHnocefHwODtuxxaHIvE0uPh_6YrE-tHiA2brYhxnO0YfO9hk-vd4z9Of79f36Z3V79-NmfXVbeSHEXGkQxBEpheNaU6u5s04T0ToCgra-EeCZlU0nCQPJC2UZ5aJtwLWtBHD8DH1dvGPqzM4HE2043k00u2Suft_fmNLgWqrCXizslOLTHvJshpDLo3o7QtxnQxtBa93UdV1QuqA-xZwTdGZKYbDpYCgxL5uYZRNTNjEvmxhWOl9e9Xs3QPvW-DdCAdgC5BKNG0jmMe7TWL7nP9a_6I2XmQ</addsrcrecordid><sourcetype>Open Website</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1841798777</pqid></control><display><type>article</type><title>Effects of CYP2C9 genetic polymorphisms on the pharmacokinetics of celecoxib and its carboxylic acid metabolite</title><source>Springer Nature</source><creator>Kim, Se-Hyung ; Kim, Do-Hoon ; Byeon, Ji-Yeong ; Kim, Young-Hoon ; Kim, Dong-Hyun ; Lim, Hye-Jin ; Lee, Choong-Min ; Whang, Sang Sup ; Choi, Chang-Ik ; Bae, Jung-Woo ; Lee, Yun Jeong ; Jang, Choon-Gon ; Lee, Seok-Yong</creator><creatorcontrib>Kim, Se-Hyung ; Kim, Do-Hoon ; Byeon, Ji-Yeong ; Kim, Young-Hoon ; Kim, Dong-Hyun ; Lim, Hye-Jin ; Lee, Choong-Min ; Whang, Sang Sup ; Choi, Chang-Ik ; Bae, Jung-Woo ; Lee, Yun Jeong ; Jang, Choon-Gon ; Lee, Seok-Yong</creatorcontrib><description>Celecoxib, a selective cyclooxygenase (COX)-2 inhibitor, is used for the treatment of rheumatoid arthritis and osteoarthritis. The predominant hepatic metabolism of celecoxib to celecoxib carboxylic acid (CCA) is mediated mainly by CYP2C9. We investigated the effects of the major
CYP2C9
genetic variants in Asian populations,
CYP2C9*3
and
CYP2C9*13
, on the pharmacokinetics of celecoxib and its carboxylic acid metabolite in healthy Korean subjects. A single 200-mg oral dose of celecoxib was given to 52 Korean subjects with different
CYP2C9
genotypes: CYP2C9EM (n = 26;
CYP2C9*1/*1
), CYP2C9IM (n = 24;
CYP2C9*1/*3
and
*1/*13
), and CYP2C9PM (n = 2;
CYP2C9*3/*3
). Celecoxib and CCA concentrations in plasma samples collected up to 48 or 96 h after drug intake were determined by HPLC–MS/MS. The mean area under the plasma concentration–time curve (AUC
0–∞
) of celecoxib was increased 1.63-fold (
P
< 0.001), and the apparent oral clearance (CL/F) of celecoxib was decreased by 39.6% in the CYP2C9IM genotype group compared with that of CYP2C9EM (
P
< 0.001). The overall pharmacokinetic parameters for celecoxib in
CYP2C9*1/*13
subjects were similar to those in
CYP2C9*1/*3
subjects. Two subjects with CYP2C9PM genotype both showed markedly higher AUC
0–∞
, prolonged half-life, and lower CL/F for celecoxib than did subjects with CYP2C9EM and IM genotypes.
CYP2C9*3
and
CYP2C9*13
variant alleles significantly affected the plasma concentration of celecoxib.</description><identifier>ISSN: 0253-6269</identifier><identifier>EISSN: 1976-3786</identifier><identifier>DOI: 10.1007/s12272-016-0861-2</identifier><identifier>PMID: 27864660</identifier><language>eng</language><publisher>Seoul: Pharmaceutical Society of Korea</publisher><subject>Alleles ; Asian Continental Ancestry Group - genetics ; Carboxylic Acids - metabolism ; Celecoxib - pharmacokinetics ; Cyclooxygenase 2 Inhibitors - pharmacokinetics ; Cytochrome P-450 CYP2C9 - genetics ; Cytochrome P-450 CYP2C9 - metabolism ; Female ; Genetic Variation ; Genotype ; Humans ; Male ; Medicine ; Pharmacology/Toxicology ; Pharmacy ; Polymorphism, Genetic ; Research Article ; Young Adult ; 약학</subject><ispartof>Archives of Pharmacal Research, 2017, 40(3), , pp.382-390</ispartof><rights>The Pharmaceutical Society of Korea 2016</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c444t-9e40b0554b3991a93bab904db0e41dc84ec2a58f502e534b3a2134d8ebdd5eeb3</citedby><cites>FETCH-LOGICAL-c444t-9e40b0554b3991a93bab904db0e41dc84ec2a58f502e534b3a2134d8ebdd5eeb3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/27864660$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://www.kci.go.kr/kciportal/ci/sereArticleSearch/ciSereArtiView.kci?sereArticleSearchBean.artiId=ART002206048$$DAccess content in National Research Foundation of Korea (NRF)$$Hfree_for_read</backlink></links><search><creatorcontrib>Kim, Se-Hyung</creatorcontrib><creatorcontrib>Kim, Do-Hoon</creatorcontrib><creatorcontrib>Byeon, Ji-Yeong</creatorcontrib><creatorcontrib>Kim, Young-Hoon</creatorcontrib><creatorcontrib>Kim, Dong-Hyun</creatorcontrib><creatorcontrib>Lim, Hye-Jin</creatorcontrib><creatorcontrib>Lee, Choong-Min</creatorcontrib><creatorcontrib>Whang, Sang Sup</creatorcontrib><creatorcontrib>Choi, Chang-Ik</creatorcontrib><creatorcontrib>Bae, Jung-Woo</creatorcontrib><creatorcontrib>Lee, Yun Jeong</creatorcontrib><creatorcontrib>Jang, Choon-Gon</creatorcontrib><creatorcontrib>Lee, Seok-Yong</creatorcontrib><title>Effects of CYP2C9 genetic polymorphisms on the pharmacokinetics of celecoxib and its carboxylic acid metabolite</title><title>Archives of pharmacal research</title><addtitle>Arch. Pharm. Res</addtitle><addtitle>Arch Pharm Res</addtitle><description>Celecoxib, a selective cyclooxygenase (COX)-2 inhibitor, is used for the treatment of rheumatoid arthritis and osteoarthritis. The predominant hepatic metabolism of celecoxib to celecoxib carboxylic acid (CCA) is mediated mainly by CYP2C9. We investigated the effects of the major
CYP2C9
genetic variants in Asian populations,
CYP2C9*3
and
CYP2C9*13
, on the pharmacokinetics of celecoxib and its carboxylic acid metabolite in healthy Korean subjects. A single 200-mg oral dose of celecoxib was given to 52 Korean subjects with different
CYP2C9
genotypes: CYP2C9EM (n = 26;
CYP2C9*1/*1
), CYP2C9IM (n = 24;
CYP2C9*1/*3
and
*1/*13
), and CYP2C9PM (n = 2;
CYP2C9*3/*3
). Celecoxib and CCA concentrations in plasma samples collected up to 48 or 96 h after drug intake were determined by HPLC–MS/MS. The mean area under the plasma concentration–time curve (AUC
0–∞
) of celecoxib was increased 1.63-fold (
P
< 0.001), and the apparent oral clearance (CL/F) of celecoxib was decreased by 39.6% in the CYP2C9IM genotype group compared with that of CYP2C9EM (
P
< 0.001). The overall pharmacokinetic parameters for celecoxib in
CYP2C9*1/*13
subjects were similar to those in
CYP2C9*1/*3
subjects. Two subjects with CYP2C9PM genotype both showed markedly higher AUC
0–∞
, prolonged half-life, and lower CL/F for celecoxib than did subjects with CYP2C9EM and IM genotypes.
CYP2C9*3
and
CYP2C9*13
variant alleles significantly affected the plasma concentration of celecoxib.</description><subject>Alleles</subject><subject>Asian Continental Ancestry Group - genetics</subject><subject>Carboxylic Acids - metabolism</subject><subject>Celecoxib - pharmacokinetics</subject><subject>Cyclooxygenase 2 Inhibitors - pharmacokinetics</subject><subject>Cytochrome P-450 CYP2C9 - genetics</subject><subject>Cytochrome P-450 CYP2C9 - metabolism</subject><subject>Female</subject><subject>Genetic Variation</subject><subject>Genotype</subject><subject>Humans</subject><subject>Male</subject><subject>Medicine</subject><subject>Pharmacology/Toxicology</subject><subject>Pharmacy</subject><subject>Polymorphism, Genetic</subject><subject>Research Article</subject><subject>Young Adult</subject><subject>약학</subject><issn>0253-6269</issn><issn>1976-3786</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><recordid>eNp9kU1P3DAURa2qVRmgP6Cbyku6CPV34iUa0RYJiaqiC1aW7bzMmEniYGck5t_XTCjLrt7innsk-yL0mZJLSkj9LVPGalYRqirSKFqxd2hFda0qXjfqPVoRJnmlmNIn6DTnR0K4klJ-RCes5EIpskLxuuvAzxnHDq8ffrG1xhsYYQ4eT7E_DDFN25CHko943gKetjYN1sddOELHnocefHwODtuxxaHIvE0uPh_6YrE-tHiA2brYhxnO0YfO9hk-vd4z9Of79f36Z3V79-NmfXVbeSHEXGkQxBEpheNaU6u5s04T0ToCgra-EeCZlU0nCQPJC2UZ5aJtwLWtBHD8DH1dvGPqzM4HE2043k00u2Suft_fmNLgWqrCXizslOLTHvJshpDLo3o7QtxnQxtBa93UdV1QuqA-xZwTdGZKYbDpYCgxL5uYZRNTNjEvmxhWOl9e9Xs3QPvW-DdCAdgC5BKNG0jmMe7TWL7nP9a_6I2XmQ</recordid><startdate>20170301</startdate><enddate>20170301</enddate><creator>Kim, Se-Hyung</creator><creator>Kim, Do-Hoon</creator><creator>Byeon, Ji-Yeong</creator><creator>Kim, Young-Hoon</creator><creator>Kim, Dong-Hyun</creator><creator>Lim, Hye-Jin</creator><creator>Lee, Choong-Min</creator><creator>Whang, Sang Sup</creator><creator>Choi, Chang-Ik</creator><creator>Bae, Jung-Woo</creator><creator>Lee, Yun Jeong</creator><creator>Jang, Choon-Gon</creator><creator>Lee, Seok-Yong</creator><general>Pharmaceutical Society of Korea</general><general>대한약학회</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><scope>ACYCR</scope></search><sort><creationdate>20170301</creationdate><title>Effects of CYP2C9 genetic polymorphisms on the pharmacokinetics of celecoxib and its carboxylic acid metabolite</title><author>Kim, Se-Hyung ; Kim, Do-Hoon ; Byeon, Ji-Yeong ; Kim, Young-Hoon ; Kim, Dong-Hyun ; Lim, Hye-Jin ; Lee, Choong-Min ; Whang, Sang Sup ; Choi, Chang-Ik ; Bae, Jung-Woo ; Lee, Yun Jeong ; Jang, Choon-Gon ; Lee, Seok-Yong</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c444t-9e40b0554b3991a93bab904db0e41dc84ec2a58f502e534b3a2134d8ebdd5eeb3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>Alleles</topic><topic>Asian Continental Ancestry Group - genetics</topic><topic>Carboxylic Acids - metabolism</topic><topic>Celecoxib - pharmacokinetics</topic><topic>Cyclooxygenase 2 Inhibitors - pharmacokinetics</topic><topic>Cytochrome P-450 CYP2C9 - genetics</topic><topic>Cytochrome P-450 CYP2C9 - metabolism</topic><topic>Female</topic><topic>Genetic Variation</topic><topic>Genotype</topic><topic>Humans</topic><topic>Male</topic><topic>Medicine</topic><topic>Pharmacology/Toxicology</topic><topic>Pharmacy</topic><topic>Polymorphism, Genetic</topic><topic>Research Article</topic><topic>Young Adult</topic><topic>약학</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Kim, Se-Hyung</creatorcontrib><creatorcontrib>Kim, Do-Hoon</creatorcontrib><creatorcontrib>Byeon, Ji-Yeong</creatorcontrib><creatorcontrib>Kim, Young-Hoon</creatorcontrib><creatorcontrib>Kim, Dong-Hyun</creatorcontrib><creatorcontrib>Lim, Hye-Jin</creatorcontrib><creatorcontrib>Lee, Choong-Min</creatorcontrib><creatorcontrib>Whang, Sang Sup</creatorcontrib><creatorcontrib>Choi, Chang-Ik</creatorcontrib><creatorcontrib>Bae, Jung-Woo</creatorcontrib><creatorcontrib>Lee, Yun Jeong</creatorcontrib><creatorcontrib>Jang, Choon-Gon</creatorcontrib><creatorcontrib>Lee, Seok-Yong</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><collection>Korean Citation Index</collection><jtitle>Archives of pharmacal research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kim, Se-Hyung</au><au>Kim, Do-Hoon</au><au>Byeon, Ji-Yeong</au><au>Kim, Young-Hoon</au><au>Kim, Dong-Hyun</au><au>Lim, Hye-Jin</au><au>Lee, Choong-Min</au><au>Whang, Sang Sup</au><au>Choi, Chang-Ik</au><au>Bae, Jung-Woo</au><au>Lee, Yun Jeong</au><au>Jang, Choon-Gon</au><au>Lee, Seok-Yong</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Effects of CYP2C9 genetic polymorphisms on the pharmacokinetics of celecoxib and its carboxylic acid metabolite</atitle><jtitle>Archives of pharmacal research</jtitle><stitle>Arch. Pharm. Res</stitle><addtitle>Arch Pharm Res</addtitle><date>2017-03-01</date><risdate>2017</risdate><volume>40</volume><issue>3</issue><spage>382</spage><epage>390</epage><pages>382-390</pages><issn>0253-6269</issn><eissn>1976-3786</eissn><abstract>Celecoxib, a selective cyclooxygenase (COX)-2 inhibitor, is used for the treatment of rheumatoid arthritis and osteoarthritis. The predominant hepatic metabolism of celecoxib to celecoxib carboxylic acid (CCA) is mediated mainly by CYP2C9. We investigated the effects of the major
CYP2C9
genetic variants in Asian populations,
CYP2C9*3
and
CYP2C9*13
, on the pharmacokinetics of celecoxib and its carboxylic acid metabolite in healthy Korean subjects. A single 200-mg oral dose of celecoxib was given to 52 Korean subjects with different
CYP2C9
genotypes: CYP2C9EM (n = 26;
CYP2C9*1/*1
), CYP2C9IM (n = 24;
CYP2C9*1/*3
and
*1/*13
), and CYP2C9PM (n = 2;
CYP2C9*3/*3
). Celecoxib and CCA concentrations in plasma samples collected up to 48 or 96 h after drug intake were determined by HPLC–MS/MS. The mean area under the plasma concentration–time curve (AUC
0–∞
) of celecoxib was increased 1.63-fold (
P
< 0.001), and the apparent oral clearance (CL/F) of celecoxib was decreased by 39.6% in the CYP2C9IM genotype group compared with that of CYP2C9EM (
P
< 0.001). The overall pharmacokinetic parameters for celecoxib in
CYP2C9*1/*13
subjects were similar to those in
CYP2C9*1/*3
subjects. Two subjects with CYP2C9PM genotype both showed markedly higher AUC
0–∞
, prolonged half-life, and lower CL/F for celecoxib than did subjects with CYP2C9EM and IM genotypes.
CYP2C9*3
and
CYP2C9*13
variant alleles significantly affected the plasma concentration of celecoxib.</abstract><cop>Seoul</cop><pub>Pharmaceutical Society of Korea</pub><pmid>27864660</pmid><doi>10.1007/s12272-016-0861-2</doi><tpages>9</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0253-6269 |
| ispartof | Archives of Pharmacal Research, 2017, 40(3), , pp.382-390 |
| issn | 0253-6269 1976-3786 |
| language | eng |
| recordid | cdi_nrf_kci_oai_kci_go_kr_ARTI_1343956 |
| source | Springer Nature |
| subjects | Alleles Asian Continental Ancestry Group - genetics Carboxylic Acids - metabolism Celecoxib - pharmacokinetics Cyclooxygenase 2 Inhibitors - pharmacokinetics Cytochrome P-450 CYP2C9 - genetics Cytochrome P-450 CYP2C9 - metabolism Female Genetic Variation Genotype Humans Male Medicine Pharmacology/Toxicology Pharmacy Polymorphism, Genetic Research Article Young Adult 약학 |
| title | Effects of CYP2C9 genetic polymorphisms on the pharmacokinetics of celecoxib and its carboxylic acid metabolite |
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