Impact of Genetic Polymorphisms on Phenytoin Pharmacokinetics and Clinical Outcomes in the Middle East and North Africa Region
Background Genetic polymorphisms are known to influence outcomes with phenytoin yet effects in the Middle East and North Africa region are poorly understood. Objectives The objective of this systematic review was to evaluate the impact of genetic polymorphisms on phenytoin pharmacokinetics and clini...
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| Veröffentlicht in: | Drugs in R&D 2017-09, Vol.17 (3), p.341-361 |
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| creator | Dagenais, Renée Wilby, Kyle John Elewa, Hazem Ensom, Mary H. H. |
| description | Background
Genetic polymorphisms are known to influence outcomes with phenytoin yet effects in the Middle East and North Africa region are poorly understood.
Objectives
The objective of this systematic review was to evaluate the impact of genetic polymorphisms on phenytoin pharmacokinetics and clinical outcomes in populations originating from the Middle East and North Africa region, and to characterize genotypic and allelic frequencies within the region for genetic polymorphisms assessed.
Methods
MEDLINE (1946–3 May, 2017), EMBASE (1974–3 May, 2017), Pharmacogenomics Knowledge Base, and Public Health Genomics Knowledge Base online databases were searched. Studies were included if genotyping and analyses of phenytoin pharmacokinetics were performed in patients of the Middle East and North Africa region. Study quality was assessed using a National Institutes of Health assessment tool. A secondary search identified studies reporting genotypic and allelic frequencies of assessed genetic polymorphisms within the Middle East and North Africa region.
Results
Five studies met the inclusion criteria.
CYP2C9
,
CYP2C19
, and multidrug resistance protein 1 C3435T variants were evaluated. While
CYP2C9*2
and
*3
variants significantly reduced phenytoin metabolism, the impacts of
CYP2C19*2
and
*3
variants were unclear. The multidrug resistance protein 1 CC genotype was associated with drug-resistant epilepsy, but reported impacts on phenytoin pharmacokinetics were conflicting. Appreciable variability in minor allele frequencies existed both between and within countries of the Middle East and North Africa region.
Conclusions
CYP2C9
decrease-of-function alleles altered phenytoin pharmacokinetics in patients originating from the Middle East and North Africa region. The impacts of
CYP2C19
and multidrug resistance protein 1 C3435T variants on phenytoin pharmacokinetic and clinical outcomes are unclear and require further investigation. Future research should focus on the clinical outcomes associated with phenytoin therapy.
PROSPERO 2017: CRD42017057850 |
| doi_str_mv | 10.1007/s40268-017-0195-7 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_5629135</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2136233336</sourcerecordid><originalsourceid>FETCH-LOGICAL-c470t-acb2c755e63c39f7b5a37baca568a91882de9d7d413910a56aaa299696a777653</originalsourceid><addsrcrecordid>eNp1kU1vEzEQhi0EoqXwA7ggS5wX_LHrjwtSFZVSqdCqgrM18XqzLrt2sB2kXPrb6ySlwKGWLI9mnnln5Beht5R8oITIj7klTKiGUFmv7hr5DB1TKnUjNKHP93HbdEqJI_Qq51tCCOVCvURHTMlW8VYdo7uLeQ224Djgcxdc8RZfx2k7x7QefZ4zjgFfjy5sS_S7CNIMNv70ezRjCD1eTD54CxO-2hQbZ5dxJcvo8Fff95PDZ5DLHvwWUxnx6ZAqjW_cysfwGr0YYMruzcN7gn58Pvu--NJcXp1fLE4vG9tKUhqwS2Zl1znBLdeDXHbA5RIsdEKBpkqx3ule9i3lmpKaBQCmtdACpJSi4yfo00F3vVnOrrculASTWSc_Q9qaCN78Xwl-NKv423SCacp3Au8fBFL8tXG5mNu4SaHubFj9VMbrEZWiB8qmmHNyw-MESszOMnOwzFTLzM4yI2vPu39Xe-z441EF2AHItRRWLv0d_bTqPdJDo5s</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2136233336</pqid></control><display><type>article</type><title>Impact of Genetic Polymorphisms on Phenytoin Pharmacokinetics and Clinical Outcomes in the Middle East and North Africa Region</title><source>MEDLINE</source><source>DOAJ Directory of Open Access Journals</source><source>Springer Nature OA Free Journals</source><source>EZB-FREE-00999 freely available EZB journals</source><source>PubMed Central</source><source>Alma/SFX Local Collection</source><creator>Dagenais, Renée ; Wilby, Kyle John ; Elewa, Hazem ; Ensom, Mary H. H.</creator><creatorcontrib>Dagenais, Renée ; Wilby, Kyle John ; Elewa, Hazem ; Ensom, Mary H. H.</creatorcontrib><description>Background
Genetic polymorphisms are known to influence outcomes with phenytoin yet effects in the Middle East and North Africa region are poorly understood.
Objectives
The objective of this systematic review was to evaluate the impact of genetic polymorphisms on phenytoin pharmacokinetics and clinical outcomes in populations originating from the Middle East and North Africa region, and to characterize genotypic and allelic frequencies within the region for genetic polymorphisms assessed.
Methods
MEDLINE (1946–3 May, 2017), EMBASE (1974–3 May, 2017), Pharmacogenomics Knowledge Base, and Public Health Genomics Knowledge Base online databases were searched. Studies were included if genotyping and analyses of phenytoin pharmacokinetics were performed in patients of the Middle East and North Africa region. Study quality was assessed using a National Institutes of Health assessment tool. A secondary search identified studies reporting genotypic and allelic frequencies of assessed genetic polymorphisms within the Middle East and North Africa region.
Results
Five studies met the inclusion criteria.
CYP2C9
,
CYP2C19
, and multidrug resistance protein 1 C3435T variants were evaluated. While
CYP2C9*2
and
*3
variants significantly reduced phenytoin metabolism, the impacts of
CYP2C19*2
and
*3
variants were unclear. The multidrug resistance protein 1 CC genotype was associated with drug-resistant epilepsy, but reported impacts on phenytoin pharmacokinetics were conflicting. Appreciable variability in minor allele frequencies existed both between and within countries of the Middle East and North Africa region.
Conclusions
CYP2C9
decrease-of-function alleles altered phenytoin pharmacokinetics in patients originating from the Middle East and North Africa region. The impacts of
CYP2C19
and multidrug resistance protein 1 C3435T variants on phenytoin pharmacokinetic and clinical outcomes are unclear and require further investigation. Future research should focus on the clinical outcomes associated with phenytoin therapy.
PROSPERO 2017: CRD42017057850</description><identifier>ISSN: 1174-5886</identifier><identifier>EISSN: 1179-6901</identifier><identifier>DOI: 10.1007/s40268-017-0195-7</identifier><identifier>PMID: 28748348</identifier><language>eng</language><publisher>Cham: Springer International Publishing</publisher><subject>Africa, Northern ; Anticonvulsants - pharmacokinetics ; Anticonvulsants - therapeutic use ; Clinical outcomes ; CRD42017057850 ; Cytochrome P-450 CYP2C19 - genetics ; Cytochrome P-450 CYP2C9 - genetics ; Epilepsy - drug therapy ; Epilepsy - genetics ; Genotype ; Humans ; Internal Medicine ; Medicine ; Medicine & Public Health ; Middle East ; Pharmacokinetics ; Pharmacology/Toxicology ; Pharmacotherapy ; Phenytoin - pharmacokinetics ; Phenytoin - therapeutic use ; Polymorphism, Genetic ; Proteins ; Systematic Review</subject><ispartof>Drugs in R&D, 2017-09, Vol.17 (3), p.341-361</ispartof><rights>The Author(s) 2017</rights><rights>Drugs in R&D is a copyright of Springer, (2017). All Rights Reserved. © 2017. This work is published under http://creativecommons.org/licenses/by-nc/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c470t-acb2c755e63c39f7b5a37baca568a91882de9d7d413910a56aaa299696a777653</citedby><cites>FETCH-LOGICAL-c470t-acb2c755e63c39f7b5a37baca568a91882de9d7d413910a56aaa299696a777653</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/PMC5629135/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5629135/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,27924,27925,41120,42189,51576,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28748348$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Dagenais, Renée</creatorcontrib><creatorcontrib>Wilby, Kyle John</creatorcontrib><creatorcontrib>Elewa, Hazem</creatorcontrib><creatorcontrib>Ensom, Mary H. H.</creatorcontrib><title>Impact of Genetic Polymorphisms on Phenytoin Pharmacokinetics and Clinical Outcomes in the Middle East and North Africa Region</title><title>Drugs in R&D</title><addtitle>Drugs R D</addtitle><addtitle>Drugs R D</addtitle><description>Background
Genetic polymorphisms are known to influence outcomes with phenytoin yet effects in the Middle East and North Africa region are poorly understood.
Objectives
The objective of this systematic review was to evaluate the impact of genetic polymorphisms on phenytoin pharmacokinetics and clinical outcomes in populations originating from the Middle East and North Africa region, and to characterize genotypic and allelic frequencies within the region for genetic polymorphisms assessed.
Methods
MEDLINE (1946–3 May, 2017), EMBASE (1974–3 May, 2017), Pharmacogenomics Knowledge Base, and Public Health Genomics Knowledge Base online databases were searched. Studies were included if genotyping and analyses of phenytoin pharmacokinetics were performed in patients of the Middle East and North Africa region. Study quality was assessed using a National Institutes of Health assessment tool. A secondary search identified studies reporting genotypic and allelic frequencies of assessed genetic polymorphisms within the Middle East and North Africa region.
Results
Five studies met the inclusion criteria.
CYP2C9
,
CYP2C19
, and multidrug resistance protein 1 C3435T variants were evaluated. While
CYP2C9*2
and
*3
variants significantly reduced phenytoin metabolism, the impacts of
CYP2C19*2
and
*3
variants were unclear. The multidrug resistance protein 1 CC genotype was associated with drug-resistant epilepsy, but reported impacts on phenytoin pharmacokinetics were conflicting. Appreciable variability in minor allele frequencies existed both between and within countries of the Middle East and North Africa region.
Conclusions
CYP2C9
decrease-of-function alleles altered phenytoin pharmacokinetics in patients originating from the Middle East and North Africa region. The impacts of
CYP2C19
and multidrug resistance protein 1 C3435T variants on phenytoin pharmacokinetic and clinical outcomes are unclear and require further investigation. Future research should focus on the clinical outcomes associated with phenytoin therapy.
PROSPERO 2017: CRD42017057850</description><subject>Africa, Northern</subject><subject>Anticonvulsants - pharmacokinetics</subject><subject>Anticonvulsants - therapeutic use</subject><subject>Clinical outcomes</subject><subject>CRD42017057850</subject><subject>Cytochrome P-450 CYP2C19 - genetics</subject><subject>Cytochrome P-450 CYP2C9 - genetics</subject><subject>Epilepsy - drug therapy</subject><subject>Epilepsy - genetics</subject><subject>Genotype</subject><subject>Humans</subject><subject>Internal Medicine</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Middle East</subject><subject>Pharmacokinetics</subject><subject>Pharmacology/Toxicology</subject><subject>Pharmacotherapy</subject><subject>Phenytoin - pharmacokinetics</subject><subject>Phenytoin - therapeutic use</subject><subject>Polymorphism, Genetic</subject><subject>Proteins</subject><subject>Systematic Review</subject><issn>1174-5886</issn><issn>1179-6901</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>C6C</sourceid><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><recordid>eNp1kU1vEzEQhi0EoqXwA7ggS5wX_LHrjwtSFZVSqdCqgrM18XqzLrt2sB2kXPrb6ySlwKGWLI9mnnln5Beht5R8oITIj7klTKiGUFmv7hr5DB1TKnUjNKHP93HbdEqJI_Qq51tCCOVCvURHTMlW8VYdo7uLeQ224Djgcxdc8RZfx2k7x7QefZ4zjgFfjy5sS_S7CNIMNv70ezRjCD1eTD54CxO-2hQbZ5dxJcvo8Fff95PDZ5DLHvwWUxnx6ZAqjW_cysfwGr0YYMruzcN7gn58Pvu--NJcXp1fLE4vG9tKUhqwS2Zl1znBLdeDXHbA5RIsdEKBpkqx3ule9i3lmpKaBQCmtdACpJSi4yfo00F3vVnOrrculASTWSc_Q9qaCN78Xwl-NKv423SCacp3Au8fBFL8tXG5mNu4SaHubFj9VMbrEZWiB8qmmHNyw-MESszOMnOwzFTLzM4yI2vPu39Xe-z441EF2AHItRRWLv0d_bTqPdJDo5s</recordid><startdate>20170901</startdate><enddate>20170901</enddate><creator>Dagenais, Renée</creator><creator>Wilby, Kyle John</creator><creator>Elewa, Hazem</creator><creator>Ensom, Mary H. H.</creator><general>Springer International Publishing</general><general>Springer Nature B.V</general><scope>C6C</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>88E</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>5PM</scope></search><sort><creationdate>20170901</creationdate><title>Impact of Genetic Polymorphisms on Phenytoin Pharmacokinetics and Clinical Outcomes in the Middle East and North Africa Region</title><author>Dagenais, Renée ; Wilby, Kyle John ; Elewa, Hazem ; Ensom, Mary H. H.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c470t-acb2c755e63c39f7b5a37baca568a91882de9d7d413910a56aaa299696a777653</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>Africa, Northern</topic><topic>Anticonvulsants - pharmacokinetics</topic><topic>Anticonvulsants - therapeutic use</topic><topic>Clinical outcomes</topic><topic>CRD42017057850</topic><topic>Cytochrome P-450 CYP2C19 - genetics</topic><topic>Cytochrome P-450 CYP2C9 - genetics</topic><topic>Epilepsy - drug therapy</topic><topic>Epilepsy - genetics</topic><topic>Genotype</topic><topic>Humans</topic><topic>Internal Medicine</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>Middle East</topic><topic>Pharmacokinetics</topic><topic>Pharmacology/Toxicology</topic><topic>Pharmacotherapy</topic><topic>Phenytoin - pharmacokinetics</topic><topic>Phenytoin - therapeutic use</topic><topic>Polymorphism, Genetic</topic><topic>Proteins</topic><topic>Systematic Review</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Dagenais, Renée</creatorcontrib><creatorcontrib>Wilby, Kyle John</creatorcontrib><creatorcontrib>Elewa, Hazem</creatorcontrib><creatorcontrib>Ensom, Mary H. H.</creatorcontrib><collection>Springer Nature OA Free Journals</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>Medical Database (Alumni Edition)</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</collection><collection>ProQuest One Community College</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>Medical 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>PubMed Central (Full Participant titles)</collection><jtitle>Drugs in R&D</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Dagenais, Renée</au><au>Wilby, Kyle John</au><au>Elewa, Hazem</au><au>Ensom, Mary H. H.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Impact of Genetic Polymorphisms on Phenytoin Pharmacokinetics and Clinical Outcomes in the Middle East and North Africa Region</atitle><jtitle>Drugs in R&D</jtitle><stitle>Drugs R D</stitle><addtitle>Drugs R D</addtitle><date>2017-09-01</date><risdate>2017</risdate><volume>17</volume><issue>3</issue><spage>341</spage><epage>361</epage><pages>341-361</pages><issn>1174-5886</issn><eissn>1179-6901</eissn><abstract>Background
Genetic polymorphisms are known to influence outcomes with phenytoin yet effects in the Middle East and North Africa region are poorly understood.
Objectives
The objective of this systematic review was to evaluate the impact of genetic polymorphisms on phenytoin pharmacokinetics and clinical outcomes in populations originating from the Middle East and North Africa region, and to characterize genotypic and allelic frequencies within the region for genetic polymorphisms assessed.
Methods
MEDLINE (1946–3 May, 2017), EMBASE (1974–3 May, 2017), Pharmacogenomics Knowledge Base, and Public Health Genomics Knowledge Base online databases were searched. Studies were included if genotyping and analyses of phenytoin pharmacokinetics were performed in patients of the Middle East and North Africa region. Study quality was assessed using a National Institutes of Health assessment tool. A secondary search identified studies reporting genotypic and allelic frequencies of assessed genetic polymorphisms within the Middle East and North Africa region.
Results
Five studies met the inclusion criteria.
CYP2C9
,
CYP2C19
, and multidrug resistance protein 1 C3435T variants were evaluated. While
CYP2C9*2
and
*3
variants significantly reduced phenytoin metabolism, the impacts of
CYP2C19*2
and
*3
variants were unclear. The multidrug resistance protein 1 CC genotype was associated with drug-resistant epilepsy, but reported impacts on phenytoin pharmacokinetics were conflicting. Appreciable variability in minor allele frequencies existed both between and within countries of the Middle East and North Africa region.
Conclusions
CYP2C9
decrease-of-function alleles altered phenytoin pharmacokinetics in patients originating from the Middle East and North Africa region. The impacts of
CYP2C19
and multidrug resistance protein 1 C3435T variants on phenytoin pharmacokinetic and clinical outcomes are unclear and require further investigation. Future research should focus on the clinical outcomes associated with phenytoin therapy.
PROSPERO 2017: CRD42017057850</abstract><cop>Cham</cop><pub>Springer International Publishing</pub><pmid>28748348</pmid><doi>10.1007/s40268-017-0195-7</doi><tpages>21</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1174-5886 |
| ispartof | Drugs in R&D, 2017-09, Vol.17 (3), p.341-361 |
| issn | 1174-5886 1179-6901 |
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| source | MEDLINE; DOAJ Directory of Open Access Journals; Springer Nature OA Free Journals; EZB-FREE-00999 freely available EZB journals; PubMed Central; Alma/SFX Local Collection |
| subjects | Africa, Northern Anticonvulsants - pharmacokinetics Anticonvulsants - therapeutic use Clinical outcomes CRD42017057850 Cytochrome P-450 CYP2C19 - genetics Cytochrome P-450 CYP2C9 - genetics Epilepsy - drug therapy Epilepsy - genetics Genotype Humans Internal Medicine Medicine Medicine & Public Health Middle East Pharmacokinetics Pharmacology/Toxicology Pharmacotherapy Phenytoin - pharmacokinetics Phenytoin - therapeutic use Polymorphism, Genetic Proteins Systematic Review |
| title | Impact of Genetic Polymorphisms on Phenytoin Pharmacokinetics and Clinical Outcomes in the Middle East and North Africa Region |
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