Pharmacogenetics of CYP3A5 on Carbamazepine pharmacokinetics in epileptic patients developing toxicity

Pharmacogenetics of CYP3A5 on Carbamazepine pharmacokinetics in epileptic patients developing toxicity

Background: The genetically polymorphic cytochrome P450 enzymes are involved in the metabolism and elimination of a number of widely used drugs. CYP3A5 exhibits remarkable inter-individual differences in the pharmacokinetics of Carbamazepine [1]. The present study was undertaken to investigate the e...

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
Veröffentlicht in:BMC genomics 2014-04, Vol.15 (S2), p.P2-P2, Article P2
Hauptverfasser: Al-Gahtany, Mubarak, Karunakaran, Gauthaman, Munisamy, Murali
Format: Artikel
Sprache:eng
Schlagworte:
Poster Presentation
Online-Zugang:Volltext
Tags: Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
container_end_page P2
container_issue S2
container_start_page P2
container_title BMC genomics
container_volume 15
creator Al-Gahtany, Mubarak
Karunakaran, Gauthaman
Munisamy, Murali
description Background: The genetically polymorphic cytochrome P450 enzymes are involved in the metabolism and elimination of a number of widely used drugs. CYP3A5 exhibits remarkable inter-individual differences in the pharmacokinetics of Carbamazepine [1]. The present study was undertaken to investigate the effects of CYP3A5 on the pharmacokinetics of antiepileptic drug Carbamazepine in the epileptic patients showing toxicity. Materials and methods: 30 epileptic individuals who had developed toxicity to carbamazepine and 30 control epileptic subjects who had not developed toxicity to carbamazepine were genotyped for CYP3A5 polymorphisms by polymerase chain reaction-restriction fragment length polymorphisms (PCR-RFLP Method). Carbamazepine plasma levels were analyzed by reversed phase HPLC method and pharmacokinetic parameters such as area under the concentration curve (AUC), maximum concentration (Cmax), time to Cmax (tmax) and half-life (t1/2) were estimated by non-compartmental analysis using PK SOLUTIONS registered software. Results: A significant correlation was observed in the frequency of homozygous CYP3A5 mutant allele (P
doi_str_mv 10.1186/1471-2164-15-S2-P2
format Article
fullrecord <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_4075510</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>1516743912</sourcerecordid><originalsourceid>FETCH-LOGICAL-b3142-b930d049aab9c0deeba0b1fea71aed198a4f9e0df30984641b4e6c71da9721793</originalsourceid><addsrcrecordid>eNp1kk9v1DAQxSMEEqXwBThZ4sIl4HGcOL4gVavyR6rESoUDJ2vsTLYuSRzsbEX76etoVxVFcPLY7zdPT08uitfA3wG0zXuQCkoBjSyhLi9FuRVPipOHx6d_zM-LFyldcw6qFfVJ0W-vMI7owo4mWrxLLPRs82NbndUsTGyD0eKIdzT7idh8ZH_6I-snlpWB5nxjMy6epiWxjm5oCHljx5bw2zu_3L4snvU4JHp1PE-L7x_Pv20-lxdfP33ZnF2UtgIpSqsr3nGpEa12vCOyyC30hAqQOtAtyl4T7_qK61Y2EqykxinoUCsBSlenxYeD77y3I3Uu54k4mDn6EeOtCejNY2XyV2YXbozkqq6BZ4Pzg4H14T8GjxUXRrOWa9ZyDdTmUpityD5vj0Fi-LWntJjRJ0fDgBOFfcogNEpWGlb0zV_oddjHKde0UkKKVlQqU-JAuRhSitQ_ZAJu1j_wrxT3P56n2A</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1512428237</pqid></control><display><type>article</type><title>Pharmacogenetics of CYP3A5 on Carbamazepine pharmacokinetics in epileptic patients developing toxicity</title><source>DOAJ Directory of Open Access Journals</source><source>SpringerLink Journals</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><source>PubMed Central</source><source>PubMed Central Open Access</source><source>Springer Nature OA Free Journals</source><creator>Al-Gahtany, Mubarak ; Karunakaran, Gauthaman ; Munisamy, Murali</creator><creatorcontrib>Al-Gahtany, Mubarak ; Karunakaran, Gauthaman ; Munisamy, Murali</creatorcontrib><description>Background: The genetically polymorphic cytochrome P450 enzymes are involved in the metabolism and elimination of a number of widely used drugs. CYP3A5 exhibits remarkable inter-individual differences in the pharmacokinetics of Carbamazepine [1]. The present study was undertaken to investigate the effects of CYP3A5 on the pharmacokinetics of antiepileptic drug Carbamazepine in the epileptic patients showing toxicity. Materials and methods: 30 epileptic individuals who had developed toxicity to carbamazepine and 30 control epileptic subjects who had not developed toxicity to carbamazepine were genotyped for CYP3A5 polymorphisms by polymerase chain reaction-restriction fragment length polymorphisms (PCR-RFLP Method). Carbamazepine plasma levels were analyzed by reversed phase HPLC method and pharmacokinetic parameters such as area under the concentration curve (AUC), maximum concentration (Cmax), time to Cmax (tmax) and half-life (t1/2) were estimated by non-compartmental analysis using PK SOLUTIONS registered software. Results: A significant correlation was observed in the frequency of homozygous CYP3A5 mutant allele (P &lt;0.01) among the carbamazepine toxicity and controls. The pharmacokinetics parameters of carbamazepine in homozygous mutant group showed longer half-life (t 1/2= 17 hrs) and less clearance rate (CL =1.5 L/hr) when compared to wild type group (t 1/2=12.8 hrs, CL = 2.9 L/hr). Conclusions: Our findings suggest that the CYP3A5 Genetic Polymorphisms plays a significant role in the steady state concentrations of carbamazepine and thereby having impact on toxicity in epileptic patients.</description><identifier>ISSN: 1471-2164</identifier><identifier>EISSN: 1471-2164</identifier><identifier>DOI: 10.1186/1471-2164-15-S2-P2</identifier><language>eng</language><publisher>London: BioMed Central</publisher><subject>Poster Presentation</subject><ispartof>BMC genomics, 2014-04, Vol.15 (S2), p.P2-P2, Article P2</ispartof><rights>2014 Al-Gahtany et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.</rights><rights>Copyright © 2014 Al-Gahtany et al; licensee BioMed Central Ltd. 2014 Al-Gahtany et al; licensee BioMed Central Ltd.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-b3142-b930d049aab9c0deeba0b1fea71aed198a4f9e0df30984641b4e6c71da9721793</citedby><cites>FETCH-LOGICAL-b3142-b930d049aab9c0deeba0b1fea71aed198a4f9e0df30984641b4e6c71da9721793</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/PMC4075510/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4075510/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,27901,27902,53766,53768</link.rule.ids></links><search><creatorcontrib>Al-Gahtany, Mubarak</creatorcontrib><creatorcontrib>Karunakaran, Gauthaman</creatorcontrib><creatorcontrib>Munisamy, Murali</creatorcontrib><title>Pharmacogenetics of CYP3A5 on Carbamazepine pharmacokinetics in epileptic patients developing toxicity</title><title>BMC genomics</title><description>Background: The genetically polymorphic cytochrome P450 enzymes are involved in the metabolism and elimination of a number of widely used drugs. CYP3A5 exhibits remarkable inter-individual differences in the pharmacokinetics of Carbamazepine [1]. The present study was undertaken to investigate the effects of CYP3A5 on the pharmacokinetics of antiepileptic drug Carbamazepine in the epileptic patients showing toxicity. Materials and methods: 30 epileptic individuals who had developed toxicity to carbamazepine and 30 control epileptic subjects who had not developed toxicity to carbamazepine were genotyped for CYP3A5 polymorphisms by polymerase chain reaction-restriction fragment length polymorphisms (PCR-RFLP Method). Carbamazepine plasma levels were analyzed by reversed phase HPLC method and pharmacokinetic parameters such as area under the concentration curve (AUC), maximum concentration (Cmax), time to Cmax (tmax) and half-life (t1/2) were estimated by non-compartmental analysis using PK SOLUTIONS registered software. Results: A significant correlation was observed in the frequency of homozygous CYP3A5 mutant allele (P &lt;0.01) among the carbamazepine toxicity and controls. The pharmacokinetics parameters of carbamazepine in homozygous mutant group showed longer half-life (t 1/2= 17 hrs) and less clearance rate (CL =1.5 L/hr) when compared to wild type group (t 1/2=12.8 hrs, CL = 2.9 L/hr). Conclusions: Our findings suggest that the CYP3A5 Genetic Polymorphisms plays a significant role in the steady state concentrations of carbamazepine and thereby having impact on toxicity in epileptic patients.</description><subject>Poster Presentation</subject><issn>1471-2164</issn><issn>1471-2164</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><sourceid>BENPR</sourceid><recordid>eNp1kk9v1DAQxSMEEqXwBThZ4sIl4HGcOL4gVavyR6rESoUDJ2vsTLYuSRzsbEX76etoVxVFcPLY7zdPT08uitfA3wG0zXuQCkoBjSyhLi9FuRVPipOHx6d_zM-LFyldcw6qFfVJ0W-vMI7owo4mWrxLLPRs82NbndUsTGyD0eKIdzT7idh8ZH_6I-snlpWB5nxjMy6epiWxjm5oCHljx5bw2zu_3L4snvU4JHp1PE-L7x_Pv20-lxdfP33ZnF2UtgIpSqsr3nGpEa12vCOyyC30hAqQOtAtyl4T7_qK61Y2EqykxinoUCsBSlenxYeD77y3I3Uu54k4mDn6EeOtCejNY2XyV2YXbozkqq6BZ4Pzg4H14T8GjxUXRrOWa9ZyDdTmUpityD5vj0Fi-LWntJjRJ0fDgBOFfcogNEpWGlb0zV_oddjHKde0UkKKVlQqU-JAuRhSitQ_ZAJu1j_wrxT3P56n2A</recordid><startdate>20140402</startdate><enddate>20140402</enddate><creator>Al-Gahtany, Mubarak</creator><creator>Karunakaran, Gauthaman</creator><creator>Munisamy, Murali</creator><general>BioMed Central</general><general>BioMed Central Ltd</general><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7QP</scope><scope>7QR</scope><scope>7SS</scope><scope>7TK</scope><scope>7U7</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8FD</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M7P</scope><scope>P64</scope><scope>PHGZM</scope><scope>PHGZT</scope><scope>PIMPY</scope><scope>PJZUB</scope><scope>PKEHL</scope><scope>PPXIY</scope><scope>PQEST</scope><scope>PQGLB</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>RC3</scope><scope>5PM</scope></search><sort><creationdate>20140402</creationdate><title>Pharmacogenetics of CYP3A5 on Carbamazepine pharmacokinetics in epileptic patients developing toxicity</title><author>Al-Gahtany, Mubarak ; Karunakaran, Gauthaman ; Munisamy, Murali</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-b3142-b930d049aab9c0deeba0b1fea71aed198a4f9e0df30984641b4e6c71da9721793</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>Poster Presentation</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Al-Gahtany, Mubarak</creatorcontrib><creatorcontrib>Karunakaran, Gauthaman</creatorcontrib><creatorcontrib>Munisamy, Murali</creatorcontrib><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Calcium &amp; Calcified Tissue Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Neurosciences Abstracts</collection><collection>Toxicology Abstracts</collection><collection>Health &amp; Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</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 One Sustainability</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>Environmental Sciences and Pollution Management</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 Central Student</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health &amp; Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health &amp; Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Biological Science Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>ProQuest Central (New)</collection><collection>ProQuest One Academic (New)</collection><collection>Publicly Available Content Database</collection><collection>ProQuest Health &amp; Medical Research Collection</collection><collection>ProQuest One Academic Middle East (New)</collection><collection>ProQuest One Health &amp; Nursing</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Applied &amp; Life Sciences</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><jtitle>BMC genomics</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Al-Gahtany, Mubarak</au><au>Karunakaran, Gauthaman</au><au>Munisamy, Murali</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Pharmacogenetics of CYP3A5 on Carbamazepine pharmacokinetics in epileptic patients developing toxicity</atitle><jtitle>BMC genomics</jtitle><date>2014-04-02</date><risdate>2014</risdate><volume>15</volume><issue>S2</issue><spage>P2</spage><epage>P2</epage><pages>P2-P2</pages><artnum>P2</artnum><issn>1471-2164</issn><eissn>1471-2164</eissn><abstract>Background: The genetically polymorphic cytochrome P450 enzymes are involved in the metabolism and elimination of a number of widely used drugs. CYP3A5 exhibits remarkable inter-individual differences in the pharmacokinetics of Carbamazepine [1]. The present study was undertaken to investigate the effects of CYP3A5 on the pharmacokinetics of antiepileptic drug Carbamazepine in the epileptic patients showing toxicity. Materials and methods: 30 epileptic individuals who had developed toxicity to carbamazepine and 30 control epileptic subjects who had not developed toxicity to carbamazepine were genotyped for CYP3A5 polymorphisms by polymerase chain reaction-restriction fragment length polymorphisms (PCR-RFLP Method). Carbamazepine plasma levels were analyzed by reversed phase HPLC method and pharmacokinetic parameters such as area under the concentration curve (AUC), maximum concentration (Cmax), time to Cmax (tmax) and half-life (t1/2) were estimated by non-compartmental analysis using PK SOLUTIONS registered software. Results: A significant correlation was observed in the frequency of homozygous CYP3A5 mutant allele (P &lt;0.01) among the carbamazepine toxicity and controls. The pharmacokinetics parameters of carbamazepine in homozygous mutant group showed longer half-life (t 1/2= 17 hrs) and less clearance rate (CL =1.5 L/hr) when compared to wild type group (t 1/2=12.8 hrs, CL = 2.9 L/hr). Conclusions: Our findings suggest that the CYP3A5 Genetic Polymorphisms plays a significant role in the steady state concentrations of carbamazepine and thereby having impact on toxicity in epileptic patients.</abstract><cop>London</cop><pub>BioMed Central</pub><doi>10.1186/1471-2164-15-S2-P2</doi><oa>free_for_read</oa></addata></record>
fulltext fulltext
identifier ISSN: 1471-2164
ispartof BMC genomics, 2014-04, Vol.15 (S2), p.P2-P2, Article P2
issn 1471-2164
1471-2164
language eng
recordid cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_4075510
source DOAJ Directory of Open Access Journals; SpringerLink Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central; PubMed Central Open Access; Springer Nature OA Free Journals
subjects Poster Presentation
title Pharmacogenetics of CYP3A5 on Carbamazepine pharmacokinetics in epileptic patients developing toxicity
url https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-19T13%3A34%3A11IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Pharmacogenetics%20of%20CYP3A5%20on%20Carbamazepine%20pharmacokinetics%20in%20epileptic%20patients%20developing%20toxicity&rft.jtitle=BMC%20genomics&rft.au=Al-Gahtany,%20Mubarak&rft.date=2014-04-02&rft.volume=15&rft.issue=S2&rft.spage=P2&rft.epage=P2&rft.pages=P2-P2&rft.artnum=P2&rft.issn=1471-2164&rft.eissn=1471-2164&rft_id=info:doi/10.1186/1471-2164-15-S2-P2&rft_dat=%3Cproquest_pubme%3E1516743912%3C/proquest_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1512428237&rft_id=info:pmid/&rfr_iscdi=true