Influence of functional polymorphisms of the MDR1 gene on vincristine pharmacokinetics in childhood acute lymphoblastic Leukemia
Objective Our objective was to investigate the effect of single nucleotide polymorphisms (SNPs) in the P‐glycoprotein MDR1 gene on vincristine pharmacokinetics and side effects in childhood acute lymphoblastic leukemia. Methods From 52 of 70 children who participated in a previous study on vincristi...
Gespeichert in:
| Veröffentlicht in: | Clinical pharmacology and therapeutics 2004-09, Vol.76 (3), p.220-229 |
|---|---|
| Hauptverfasser: | , , , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 229 |
|---|---|
| container_issue | 3 |
| container_start_page | 220 |
| container_title | Clinical pharmacology and therapeutics |
| container_volume | 76 |
| creator | Plasschaert, Sabine L. A. Groninger, Ellis Boezen, Marike Kema, Ido Vries, Elisabeth G. E. Uges, Donald Veerman, Anjo J. P. Kamps, Willem A. Vellenga, Edo Graaf, Siebold S. Bont, Eveline S. J. M. |
| description | Objective
Our objective was to investigate the effect of single nucleotide polymorphisms (SNPs) in the P‐glycoprotein MDR1 gene on vincristine pharmacokinetics and side effects in childhood acute lymphoblastic leukemia.
Methods
From 52 of 70 children who participated in a previous study on vincristine pharmacokinetics, patient material was available for investigation of the MDR1 genetic variants. The SNPs C3435T and G2677T were determined by use of polymerase chain reaction–restriction fragment length polymorphism. Vincristine side effects were scored retrospectively from patient records.
Results
No association was observed between C3435T or G2677T and vincristine pharmacokinetic variables. When haplotypes were assigned, haplotype 1/1 carriers (3435C/2677G) showed a longer elimination half‐life than noncarriers (1156 versus 805 minutes, P = .038). In contrast, haplotype 1/2 carriers (3435T/2677G) had a shorter elimination half‐life than noncarriers (805 versus 1180 minutes, P = .044). However, this significance was lost after Bonferroni correction for multiple testing. The haplotypes did not affect the other pharmacokinetic parameters, such as clearance and area under the concentration‐time curve, suggesting that the observed effect on elimination half‐life is of very limited relevance. Moreover, SNPs in the MDR1 gene did not identify patients with an increased risk for vincristine‐induced constipation.
Conclusion
The genetic variants in the MDR1 gene alone cannot explain the large variability in vincristine pharmacokinetics.
Clinical Pharmacology & Therapeutics (2004) 76, 220–229; doi: 10.1016/j.clpt.2004.05.007 |
| doi_str_mv | 10.1016/j.clpt.2004.05.007 |
| format | Article |
| fullrecord | <record><control><sourceid>wiley_pubme</sourceid><recordid>TN_cdi_pubmed_primary_15371983</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>CPTCLPT2004484</sourcerecordid><originalsourceid>FETCH-LOGICAL-p2924-e638f3d51abe8af31e56db741a703ea86c92ac0a133797ac076f2381cf799dc73</originalsourceid><addsrcrecordid>eNpFkUFP3DAQha0KBFvKH-gB-cIxqR0nsX1BQgu0SFuB0PZszTo28eI4UZwU7Y2fXkdQcZp5M9-8wzyEvlOSU0LrH_tc-2HKC0LKnFQ5IfwLWtGKFVldseoIrQghMpMFq0_R1xj3SZZSiBN0miBOpWAr9HYfrJ9N0Ab3Fts56Mn1ATween_o-nFoXezisptag3_fPFH8bEKCA_7rgh5dnFySQwtjB7p_SWJyOmIXsG6db9q-bzDoeTI4-Q1tv_OQTjTemPnFdA6-oWMLPprzj3qG_tzdbte_ss3Dz_v19SYbClmUmamZsKypKOyMAMuoqepmx0sKnDADotayAE2AMsYlTx2vbcEE1ZZL2WjOztDFu-8w7zrTqGF0HYwH9f8VCbj8ACBq8HaEoF385GoimSiqxF29c6_Om8PnnqglFLVXSyhqCUWRSqVQ1Ppxu948bpdRKUr2D-CrhLM</addsrcrecordid><sourcetype>Index Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype></control><display><type>article</type><title>Influence of functional polymorphisms of the MDR1 gene on vincristine pharmacokinetics in childhood acute lymphoblastic Leukemia</title><source>MEDLINE</source><source>Wiley Online Library Journals Frontfile Complete</source><creator>Plasschaert, Sabine L. A. ; Groninger, Ellis ; Boezen, Marike ; Kema, Ido ; Vries, Elisabeth G. E. ; Uges, Donald ; Veerman, Anjo J. P. ; Kamps, Willem A. ; Vellenga, Edo ; Graaf, Siebold S. ; Bont, Eveline S. J. M.</creator><creatorcontrib>Plasschaert, Sabine L. A. ; Groninger, Ellis ; Boezen, Marike ; Kema, Ido ; Vries, Elisabeth G. E. ; Uges, Donald ; Veerman, Anjo J. P. ; Kamps, Willem A. ; Vellenga, Edo ; Graaf, Siebold S. ; Bont, Eveline S. J. M.</creatorcontrib><description>Objective
Our objective was to investigate the effect of single nucleotide polymorphisms (SNPs) in the P‐glycoprotein MDR1 gene on vincristine pharmacokinetics and side effects in childhood acute lymphoblastic leukemia.
Methods
From 52 of 70 children who participated in a previous study on vincristine pharmacokinetics, patient material was available for investigation of the MDR1 genetic variants. The SNPs C3435T and G2677T were determined by use of polymerase chain reaction–restriction fragment length polymorphism. Vincristine side effects were scored retrospectively from patient records.
Results
No association was observed between C3435T or G2677T and vincristine pharmacokinetic variables. When haplotypes were assigned, haplotype 1/1 carriers (3435C/2677G) showed a longer elimination half‐life than noncarriers (1156 versus 805 minutes, P = .038). In contrast, haplotype 1/2 carriers (3435T/2677G) had a shorter elimination half‐life than noncarriers (805 versus 1180 minutes, P = .044). However, this significance was lost after Bonferroni correction for multiple testing. The haplotypes did not affect the other pharmacokinetic parameters, such as clearance and area under the concentration‐time curve, suggesting that the observed effect on elimination half‐life is of very limited relevance. Moreover, SNPs in the MDR1 gene did not identify patients with an increased risk for vincristine‐induced constipation.
Conclusion
The genetic variants in the MDR1 gene alone cannot explain the large variability in vincristine pharmacokinetics.
Clinical Pharmacology & Therapeutics (2004) 76, 220–229; doi: 10.1016/j.clpt.2004.05.007</description><identifier>ISSN: 0009-9236</identifier><identifier>EISSN: 1532-6535</identifier><identifier>DOI: 10.1016/j.clpt.2004.05.007</identifier><identifier>PMID: 15371983</identifier><identifier>CODEN: CLPTAT</identifier><language>eng</language><publisher>New York, NY: Nature Publishing</publisher><subject>Adolescent ; Antineoplastic agents ; Biological and medical sciences ; Chemotherapy ; Child ; Child, Preschool ; Cytochrome P-450 CYP3A ; Cytochrome P-450 Enzyme System - physiology ; Female ; Genes, MDR ; Haplotypes ; Humans ; Infant ; Male ; Medical sciences ; Pharmacology. Drug treatments ; Polymorphism, Genetic ; Polymorphism, Single Nucleotide ; Precursor Cell Lymphoblastic Leukemia-Lymphoma - drug therapy ; Retrospective Studies ; Vincristine - adverse effects ; Vincristine - pharmacokinetics</subject><ispartof>Clinical pharmacology and therapeutics, 2004-09, Vol.76 (3), p.220-229</ispartof><rights>2004 American Society for Clinical Pharmacology and Therapeutics</rights><rights>2005 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1016%2Fj.clpt.2004.05.007$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1016%2Fj.clpt.2004.05.007$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,776,780,1411,27901,27902,45550,45551</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=16093825$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/15371983$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Plasschaert, Sabine L. A.</creatorcontrib><creatorcontrib>Groninger, Ellis</creatorcontrib><creatorcontrib>Boezen, Marike</creatorcontrib><creatorcontrib>Kema, Ido</creatorcontrib><creatorcontrib>Vries, Elisabeth G. E.</creatorcontrib><creatorcontrib>Uges, Donald</creatorcontrib><creatorcontrib>Veerman, Anjo J. P.</creatorcontrib><creatorcontrib>Kamps, Willem A.</creatorcontrib><creatorcontrib>Vellenga, Edo</creatorcontrib><creatorcontrib>Graaf, Siebold S.</creatorcontrib><creatorcontrib>Bont, Eveline S. J. M.</creatorcontrib><title>Influence of functional polymorphisms of the MDR1 gene on vincristine pharmacokinetics in childhood acute lymphoblastic Leukemia</title><title>Clinical pharmacology and therapeutics</title><addtitle>Clin Pharmacol Ther</addtitle><description>Objective
Our objective was to investigate the effect of single nucleotide polymorphisms (SNPs) in the P‐glycoprotein MDR1 gene on vincristine pharmacokinetics and side effects in childhood acute lymphoblastic leukemia.
Methods
From 52 of 70 children who participated in a previous study on vincristine pharmacokinetics, patient material was available for investigation of the MDR1 genetic variants. The SNPs C3435T and G2677T were determined by use of polymerase chain reaction–restriction fragment length polymorphism. Vincristine side effects were scored retrospectively from patient records.
Results
No association was observed between C3435T or G2677T and vincristine pharmacokinetic variables. When haplotypes were assigned, haplotype 1/1 carriers (3435C/2677G) showed a longer elimination half‐life than noncarriers (1156 versus 805 minutes, P = .038). In contrast, haplotype 1/2 carriers (3435T/2677G) had a shorter elimination half‐life than noncarriers (805 versus 1180 minutes, P = .044). However, this significance was lost after Bonferroni correction for multiple testing. The haplotypes did not affect the other pharmacokinetic parameters, such as clearance and area under the concentration‐time curve, suggesting that the observed effect on elimination half‐life is of very limited relevance. Moreover, SNPs in the MDR1 gene did not identify patients with an increased risk for vincristine‐induced constipation.
Conclusion
The genetic variants in the MDR1 gene alone cannot explain the large variability in vincristine pharmacokinetics.
Clinical Pharmacology & Therapeutics (2004) 76, 220–229; doi: 10.1016/j.clpt.2004.05.007</description><subject>Adolescent</subject><subject>Antineoplastic agents</subject><subject>Biological and medical sciences</subject><subject>Chemotherapy</subject><subject>Child</subject><subject>Child, Preschool</subject><subject>Cytochrome P-450 CYP3A</subject><subject>Cytochrome P-450 Enzyme System - physiology</subject><subject>Female</subject><subject>Genes, MDR</subject><subject>Haplotypes</subject><subject>Humans</subject><subject>Infant</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Pharmacology. Drug treatments</subject><subject>Polymorphism, Genetic</subject><subject>Polymorphism, Single Nucleotide</subject><subject>Precursor Cell Lymphoblastic Leukemia-Lymphoma - drug therapy</subject><subject>Retrospective Studies</subject><subject>Vincristine - adverse effects</subject><subject>Vincristine - pharmacokinetics</subject><issn>0009-9236</issn><issn>1532-6535</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2004</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpFkUFP3DAQha0KBFvKH-gB-cIxqR0nsX1BQgu0SFuB0PZszTo28eI4UZwU7Y2fXkdQcZp5M9-8wzyEvlOSU0LrH_tc-2HKC0LKnFQ5IfwLWtGKFVldseoIrQghMpMFq0_R1xj3SZZSiBN0miBOpWAr9HYfrJ9N0Ab3Fts56Mn1ATween_o-nFoXezisptag3_fPFH8bEKCA_7rgh5dnFySQwtjB7p_SWJyOmIXsG6db9q-bzDoeTI4-Q1tv_OQTjTemPnFdA6-oWMLPprzj3qG_tzdbte_ss3Dz_v19SYbClmUmamZsKypKOyMAMuoqepmx0sKnDADotayAE2AMsYlTx2vbcEE1ZZL2WjOztDFu-8w7zrTqGF0HYwH9f8VCbj8ACBq8HaEoF385GoimSiqxF29c6_Om8PnnqglFLVXSyhqCUWRSqVQ1Ppxu948bpdRKUr2D-CrhLM</recordid><startdate>200409</startdate><enddate>200409</enddate><creator>Plasschaert, Sabine L. A.</creator><creator>Groninger, Ellis</creator><creator>Boezen, Marike</creator><creator>Kema, Ido</creator><creator>Vries, Elisabeth G. E.</creator><creator>Uges, Donald</creator><creator>Veerman, Anjo J. P.</creator><creator>Kamps, Willem A.</creator><creator>Vellenga, Edo</creator><creator>Graaf, Siebold S.</creator><creator>Bont, Eveline S. J. M.</creator><general>Nature Publishing</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope></search><sort><creationdate>200409</creationdate><title>Influence of functional polymorphisms of the MDR1 gene on vincristine pharmacokinetics in childhood acute lymphoblastic Leukemia</title><author>Plasschaert, Sabine L. A. ; Groninger, Ellis ; Boezen, Marike ; Kema, Ido ; Vries, Elisabeth G. E. ; Uges, Donald ; Veerman, Anjo J. P. ; Kamps, Willem A. ; Vellenga, Edo ; Graaf, Siebold S. ; Bont, Eveline S. J. M.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-p2924-e638f3d51abe8af31e56db741a703ea86c92ac0a133797ac076f2381cf799dc73</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2004</creationdate><topic>Adolescent</topic><topic>Antineoplastic agents</topic><topic>Biological and medical sciences</topic><topic>Chemotherapy</topic><topic>Child</topic><topic>Child, Preschool</topic><topic>Cytochrome P-450 CYP3A</topic><topic>Cytochrome P-450 Enzyme System - physiology</topic><topic>Female</topic><topic>Genes, MDR</topic><topic>Haplotypes</topic><topic>Humans</topic><topic>Infant</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Pharmacology. Drug treatments</topic><topic>Polymorphism, Genetic</topic><topic>Polymorphism, Single Nucleotide</topic><topic>Precursor Cell Lymphoblastic Leukemia-Lymphoma - drug therapy</topic><topic>Retrospective Studies</topic><topic>Vincristine - adverse effects</topic><topic>Vincristine - pharmacokinetics</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Plasschaert, Sabine L. A.</creatorcontrib><creatorcontrib>Groninger, Ellis</creatorcontrib><creatorcontrib>Boezen, Marike</creatorcontrib><creatorcontrib>Kema, Ido</creatorcontrib><creatorcontrib>Vries, Elisabeth G. E.</creatorcontrib><creatorcontrib>Uges, Donald</creatorcontrib><creatorcontrib>Veerman, Anjo J. P.</creatorcontrib><creatorcontrib>Kamps, Willem A.</creatorcontrib><creatorcontrib>Vellenga, Edo</creatorcontrib><creatorcontrib>Graaf, Siebold S.</creatorcontrib><creatorcontrib>Bont, Eveline S. J. M.</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><jtitle>Clinical pharmacology and therapeutics</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Plasschaert, Sabine L. A.</au><au>Groninger, Ellis</au><au>Boezen, Marike</au><au>Kema, Ido</au><au>Vries, Elisabeth G. E.</au><au>Uges, Donald</au><au>Veerman, Anjo J. P.</au><au>Kamps, Willem A.</au><au>Vellenga, Edo</au><au>Graaf, Siebold S.</au><au>Bont, Eveline S. J. M.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Influence of functional polymorphisms of the MDR1 gene on vincristine pharmacokinetics in childhood acute lymphoblastic Leukemia</atitle><jtitle>Clinical pharmacology and therapeutics</jtitle><addtitle>Clin Pharmacol Ther</addtitle><date>2004-09</date><risdate>2004</risdate><volume>76</volume><issue>3</issue><spage>220</spage><epage>229</epage><pages>220-229</pages><issn>0009-9236</issn><eissn>1532-6535</eissn><coden>CLPTAT</coden><abstract>Objective
Our objective was to investigate the effect of single nucleotide polymorphisms (SNPs) in the P‐glycoprotein MDR1 gene on vincristine pharmacokinetics and side effects in childhood acute lymphoblastic leukemia.
Methods
From 52 of 70 children who participated in a previous study on vincristine pharmacokinetics, patient material was available for investigation of the MDR1 genetic variants. The SNPs C3435T and G2677T were determined by use of polymerase chain reaction–restriction fragment length polymorphism. Vincristine side effects were scored retrospectively from patient records.
Results
No association was observed between C3435T or G2677T and vincristine pharmacokinetic variables. When haplotypes were assigned, haplotype 1/1 carriers (3435C/2677G) showed a longer elimination half‐life than noncarriers (1156 versus 805 minutes, P = .038). In contrast, haplotype 1/2 carriers (3435T/2677G) had a shorter elimination half‐life than noncarriers (805 versus 1180 minutes, P = .044). However, this significance was lost after Bonferroni correction for multiple testing. The haplotypes did not affect the other pharmacokinetic parameters, such as clearance and area under the concentration‐time curve, suggesting that the observed effect on elimination half‐life is of very limited relevance. Moreover, SNPs in the MDR1 gene did not identify patients with an increased risk for vincristine‐induced constipation.
Conclusion
The genetic variants in the MDR1 gene alone cannot explain the large variability in vincristine pharmacokinetics.
Clinical Pharmacology & Therapeutics (2004) 76, 220–229; doi: 10.1016/j.clpt.2004.05.007</abstract><cop>New York, NY</cop><pub>Nature Publishing</pub><pmid>15371983</pmid><doi>10.1016/j.clpt.2004.05.007</doi><tpages>10</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0009-9236 |
| ispartof | Clinical pharmacology and therapeutics, 2004-09, Vol.76 (3), p.220-229 |
| issn | 0009-9236 1532-6535 |
| language | eng |
| recordid | cdi_pubmed_primary_15371983 |
| source | MEDLINE; Wiley Online Library Journals Frontfile Complete |
| subjects | Adolescent Antineoplastic agents Biological and medical sciences Chemotherapy Child Child, Preschool Cytochrome P-450 CYP3A Cytochrome P-450 Enzyme System - physiology Female Genes, MDR Haplotypes Humans Infant Male Medical sciences Pharmacology. Drug treatments Polymorphism, Genetic Polymorphism, Single Nucleotide Precursor Cell Lymphoblastic Leukemia-Lymphoma - drug therapy Retrospective Studies Vincristine - adverse effects Vincristine - pharmacokinetics |
| title | Influence of functional polymorphisms of the MDR1 gene on vincristine pharmacokinetics in childhood acute lymphoblastic Leukemia |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-15T08%3A47%3A09IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-wiley_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Influence%20of%20functional%20polymorphisms%20of%20the%20MDR1%20gene%20on%20vincristine%20pharmacokinetics%20in%20childhood%20acute%20lymphoblastic%20Leukemia&rft.jtitle=Clinical%20pharmacology%20and%20therapeutics&rft.au=Plasschaert,%20Sabine%20L.%20A.&rft.date=2004-09&rft.volume=76&rft.issue=3&rft.spage=220&rft.epage=229&rft.pages=220-229&rft.issn=0009-9236&rft.eissn=1532-6535&rft.coden=CLPTAT&rft_id=info:doi/10.1016/j.clpt.2004.05.007&rft_dat=%3Cwiley_pubme%3ECPTCLPT2004484%3C/wiley_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_id=info:pmid/15371983&rfr_iscdi=true |