Effect of smoking and CYP2D6 polymorphisms on the extent of fluvoxamine-alprazolam interaction in patients with psychosomatic disease
Purpose Fluvoxamine (FVX) is metabolized by cytochrome P450 (CYP) 2D6 and CYP1A2 and inhibits CYP3A4. The aim of this study was to investigate the factors responsible for interindividual variability in the extent of interaction between FVX and alprazolam (ALP). Methods Blood samples were taken from...
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| Veröffentlicht in: | European journal of clinical pharmacology 2009-07, Vol.65 (7), p.699-704 |
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| creator | Sugahara, Hideyo Maebara, Chiharu Ohtani, Hisakazu Handa, Masanori Ando, Katsumi Mine, Kazunori Kubo, Chiharu Ieiri, Ichiro Sawada, Yasufumi |
| description | Purpose Fluvoxamine (FVX) is metabolized by cytochrome P450 (CYP) 2D6 and CYP1A2 and inhibits CYP3A4. The aim of this study was to investigate the factors responsible for interindividual variability in the extent of interaction between FVX and alprazolam (ALP). Methods Blood samples were taken from 49 depressive patients to determine plasma concentration of FVX, ALP or both. Twenty-four samples were taken during the FVX-alone period, 21 samples during the ALP-alone period and 30 samples during the FVX-ALP period. Subjects were also genotyped for CYP2D6. Results The concentration-to-dose (C/D) ratio of ALP during the FVX-treatment period was significantly higher than that during the ALP-alone period. The CYP2D6 genotype affected neither the C/D ratios of FVX nor the extent of interaction. The mean C/D ratio of FVX in smokers was reduced by more than 30% in comparison with that in non-smokers. The mean C/D ratio of ALP in non-smokers was increased by FVX, while that in smokers was unchanged. Conclusions The extent of interaction between FVX and ALP may be affected by smoking, which alters the C/D ratio of FVX. Therefore, when FVX and ALP are concomitantly administered, it should be noted that non-smokers may exhibit greater drug interaction than smokers. |
| doi_str_mv | 10.1007/s00228-009-0629-4 |
| format | Article |
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The aim of this study was to investigate the factors responsible for interindividual variability in the extent of interaction between FVX and alprazolam (ALP). Methods Blood samples were taken from 49 depressive patients to determine plasma concentration of FVX, ALP or both. Twenty-four samples were taken during the FVX-alone period, 21 samples during the ALP-alone period and 30 samples during the FVX-ALP period. Subjects were also genotyped for CYP2D6. Results The concentration-to-dose (C/D) ratio of ALP during the FVX-treatment period was significantly higher than that during the ALP-alone period. The CYP2D6 genotype affected neither the C/D ratios of FVX nor the extent of interaction. The mean C/D ratio of FVX in smokers was reduced by more than 30% in comparison with that in non-smokers. The mean C/D ratio of ALP in non-smokers was increased by FVX, while that in smokers was unchanged. Conclusions The extent of interaction between FVX and ALP may be affected by smoking, which alters the C/D ratio of FVX. Therefore, when FVX and ALP are concomitantly administered, it should be noted that non-smokers may exhibit greater drug interaction than smokers.</description><identifier>ISSN: 0031-6970</identifier><identifier>EISSN: 1432-1041</identifier><identifier>DOI: 10.1007/s00228-009-0629-4</identifier><identifier>PMID: 19225771</identifier><language>eng</language><publisher>Berlin/Heidelberg: Berlin/Heidelberg : Springer-Verlag</publisher><subject>Adult and adolescent clinical studies ; Alleles ; Alprazolam ; Alprazolam - blood ; Alprazolam - therapeutic use ; Antidepressants ; Biological and medical sciences ; Biomedical and Life Sciences ; Biomedicine ; CYP2D6 ; Cytochrome P-450 CYP2D6 - genetics ; Dose-Response Relationship, Drug ; Drug interaction ; Drug Interactions - genetics ; Fluvoxamine ; Fluvoxamine - blood ; Fluvoxamine - therapeutic use ; Genotype ; Genotype & phenotype ; Humans ; Medical sciences ; Pharmacokinectics and Disposition ; Pharmacology ; Pharmacology. Drug treatments ; Pharmacology/Toxicology ; Polymorphism ; Polymorphism, Genetic - drug effects ; Psychology. Psychoanalysis. Psychiatry ; Psychopathology. Psychiatry ; Psychophysiologic Disorders - drug therapy ; Psychophysiologic Disorders - genetics ; Psychotropic drugs ; Serotonin Uptake Inhibitors - blood ; Serotonin Uptake Inhibitors - therapeutic use ; Smoking ; Smoking - metabolism ; Somatoform disorders. Psychosomatics ; Tobacco, tobacco smoking ; Toxicology</subject><ispartof>European journal of clinical pharmacology, 2009-07, Vol.65 (7), p.699-704</ispartof><rights>Springer-Verlag 2009</rights><rights>2009 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c423t-f6fb75d95b84d090a499f0ccb1f131968fd56f6ac9434676a14100562fa2b47f3</citedby><cites>FETCH-LOGICAL-c423t-f6fb75d95b84d090a499f0ccb1f131968fd56f6ac9434676a14100562fa2b47f3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s00228-009-0629-4$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s00228-009-0629-4$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,776,780,27901,27902,41464,42533,51294</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=21669816$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/19225771$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Sugahara, Hideyo</creatorcontrib><creatorcontrib>Maebara, Chiharu</creatorcontrib><creatorcontrib>Ohtani, Hisakazu</creatorcontrib><creatorcontrib>Handa, Masanori</creatorcontrib><creatorcontrib>Ando, Katsumi</creatorcontrib><creatorcontrib>Mine, Kazunori</creatorcontrib><creatorcontrib>Kubo, Chiharu</creatorcontrib><creatorcontrib>Ieiri, Ichiro</creatorcontrib><creatorcontrib>Sawada, Yasufumi</creatorcontrib><title>Effect of smoking and CYP2D6 polymorphisms on the extent of fluvoxamine-alprazolam interaction in patients with psychosomatic disease</title><title>European journal of clinical pharmacology</title><addtitle>Eur J Clin Pharmacol</addtitle><addtitle>Eur J Clin Pharmacol</addtitle><description>Purpose Fluvoxamine (FVX) is metabolized by cytochrome P450 (CYP) 2D6 and CYP1A2 and inhibits CYP3A4. The aim of this study was to investigate the factors responsible for interindividual variability in the extent of interaction between FVX and alprazolam (ALP). Methods Blood samples were taken from 49 depressive patients to determine plasma concentration of FVX, ALP or both. Twenty-four samples were taken during the FVX-alone period, 21 samples during the ALP-alone period and 30 samples during the FVX-ALP period. Subjects were also genotyped for CYP2D6. Results The concentration-to-dose (C/D) ratio of ALP during the FVX-treatment period was significantly higher than that during the ALP-alone period. The CYP2D6 genotype affected neither the C/D ratios of FVX nor the extent of interaction. The mean C/D ratio of FVX in smokers was reduced by more than 30% in comparison with that in non-smokers. The mean C/D ratio of ALP in non-smokers was increased by FVX, while that in smokers was unchanged. Conclusions The extent of interaction between FVX and ALP may be affected by smoking, which alters the C/D ratio of FVX. Therefore, when FVX and ALP are concomitantly administered, it should be noted that non-smokers may exhibit greater drug interaction than smokers.</description><subject>Adult and adolescent clinical studies</subject><subject>Alleles</subject><subject>Alprazolam</subject><subject>Alprazolam - blood</subject><subject>Alprazolam - therapeutic use</subject><subject>Antidepressants</subject><subject>Biological and medical sciences</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>CYP2D6</subject><subject>Cytochrome P-450 CYP2D6 - genetics</subject><subject>Dose-Response Relationship, Drug</subject><subject>Drug interaction</subject><subject>Drug Interactions - genetics</subject><subject>Fluvoxamine</subject><subject>Fluvoxamine - blood</subject><subject>Fluvoxamine - therapeutic use</subject><subject>Genotype</subject><subject>Genotype & phenotype</subject><subject>Humans</subject><subject>Medical sciences</subject><subject>Pharmacokinectics and Disposition</subject><subject>Pharmacology</subject><subject>Pharmacology. Drug treatments</subject><subject>Pharmacology/Toxicology</subject><subject>Polymorphism</subject><subject>Polymorphism, Genetic - drug effects</subject><subject>Psychology. Psychoanalysis. Psychiatry</subject><subject>Psychopathology. Psychiatry</subject><subject>Psychophysiologic Disorders - drug therapy</subject><subject>Psychophysiologic Disorders - genetics</subject><subject>Psychotropic drugs</subject><subject>Serotonin Uptake Inhibitors - blood</subject><subject>Serotonin Uptake Inhibitors - therapeutic use</subject><subject>Smoking</subject><subject>Smoking - metabolism</subject><subject>Somatoform disorders. Psychosomatics</subject><subject>Tobacco, tobacco smoking</subject><subject>Toxicology</subject><issn>0031-6970</issn><issn>1432-1041</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2009</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNp9kM-P1CAYhonRuOPqH-BFiYnH6vdRSoejmV1_JJtoonvwRCiFGdYWKnR0x7v_t4yduDdPJPC870seQp4ivEKA9nUGYGxdAcgKBJMVv0dWyGtWIXC8T1YANVZCtnBGHuV8A4CNhPohOUPJWNO2uCK_L52zZqbR0TzGbz5sqQ493Xz9xC4EneJwGGOadj6PmcZA552l9na24W_CDfsf8VaPPthKD1PSv-KgR-rDbJM2sy8BH-ikZ18Cmf70845O-WB2Mcex3Bra-2x1to_JA6eHbJ-cznNy_fbyy-Z9dfXx3YfNm6vKcFbPlROua5teNt2a9yBBcykdGNOhwxqlWLu-EU5oI3nNRSs08uKpEcxp1vHW1efkxdI7pfh9b_OsbuI-hTKpGHK-xqYRBcIFMinmnKxTU_KjTgeFoI7e1eJdFe_q6F3xknl2Kt53o-3vEifRBXh5AnQ2enBJB-PzP46hEHKNx3G2cLk8ha1Ndz_83_rzJeR0VHqbSvH1ZwZYAwrOOGvqP1uZpUw</recordid><startdate>20090701</startdate><enddate>20090701</enddate><creator>Sugahara, Hideyo</creator><creator>Maebara, Chiharu</creator><creator>Ohtani, Hisakazu</creator><creator>Handa, Masanori</creator><creator>Ando, Katsumi</creator><creator>Mine, Kazunori</creator><creator>Kubo, Chiharu</creator><creator>Ieiri, Ichiro</creator><creator>Sawada, Yasufumi</creator><general>Berlin/Heidelberg : Springer-Verlag</general><general>Springer-Verlag</general><general>Springer</general><general>Springer Nature B.V</general><scope>FBQ</scope><scope>IQODW</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>7RV</scope><scope>7TK</scope><scope>7U9</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</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>H94</scope><scope>K9.</scope><scope>KB0</scope><scope>M0S</scope><scope>M1P</scope><scope>NAPCQ</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope></search><sort><creationdate>20090701</creationdate><title>Effect of smoking and CYP2D6 polymorphisms on the extent of fluvoxamine-alprazolam interaction in patients with psychosomatic disease</title><author>Sugahara, Hideyo ; Maebara, Chiharu ; Ohtani, Hisakazu ; Handa, Masanori ; Ando, Katsumi ; Mine, Kazunori ; Kubo, Chiharu ; Ieiri, Ichiro ; Sawada, Yasufumi</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c423t-f6fb75d95b84d090a499f0ccb1f131968fd56f6ac9434676a14100562fa2b47f3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2009</creationdate><topic>Adult and adolescent clinical studies</topic><topic>Alleles</topic><topic>Alprazolam</topic><topic>Alprazolam - blood</topic><topic>Alprazolam - therapeutic use</topic><topic>Antidepressants</topic><topic>Biological and medical sciences</topic><topic>Biomedical and Life Sciences</topic><topic>Biomedicine</topic><topic>CYP2D6</topic><topic>Cytochrome P-450 CYP2D6 - genetics</topic><topic>Dose-Response Relationship, Drug</topic><topic>Drug interaction</topic><topic>Drug Interactions - genetics</topic><topic>Fluvoxamine</topic><topic>Fluvoxamine - blood</topic><topic>Fluvoxamine - therapeutic use</topic><topic>Genotype</topic><topic>Genotype & phenotype</topic><topic>Humans</topic><topic>Medical sciences</topic><topic>Pharmacokinectics and Disposition</topic><topic>Pharmacology</topic><topic>Pharmacology. Drug treatments</topic><topic>Pharmacology/Toxicology</topic><topic>Polymorphism</topic><topic>Polymorphism, Genetic - drug effects</topic><topic>Psychology. Psychoanalysis. Psychiatry</topic><topic>Psychopathology. Psychiatry</topic><topic>Psychophysiologic Disorders - drug therapy</topic><topic>Psychophysiologic Disorders - genetics</topic><topic>Psychotropic drugs</topic><topic>Serotonin Uptake Inhibitors - blood</topic><topic>Serotonin Uptake Inhibitors - therapeutic use</topic><topic>Smoking</topic><topic>Smoking - metabolism</topic><topic>Somatoform disorders. Psychosomatics</topic><topic>Tobacco, tobacco smoking</topic><topic>Toxicology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Sugahara, Hideyo</creatorcontrib><creatorcontrib>Maebara, Chiharu</creatorcontrib><creatorcontrib>Ohtani, Hisakazu</creatorcontrib><creatorcontrib>Handa, Masanori</creatorcontrib><creatorcontrib>Ando, Katsumi</creatorcontrib><creatorcontrib>Mine, Kazunori</creatorcontrib><creatorcontrib>Kubo, Chiharu</creatorcontrib><creatorcontrib>Ieiri, Ichiro</creatorcontrib><creatorcontrib>Sawada, Yasufumi</creatorcontrib><collection>AGRIS</collection><collection>Pascal-Francis</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>Nursing & Allied Health Database</collection><collection>Neurosciences Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma 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 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>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Nursing & Allied Health Premium</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><jtitle>European journal of clinical pharmacology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Sugahara, Hideyo</au><au>Maebara, Chiharu</au><au>Ohtani, Hisakazu</au><au>Handa, Masanori</au><au>Ando, Katsumi</au><au>Mine, Kazunori</au><au>Kubo, Chiharu</au><au>Ieiri, Ichiro</au><au>Sawada, Yasufumi</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Effect of smoking and CYP2D6 polymorphisms on the extent of fluvoxamine-alprazolam interaction in patients with psychosomatic disease</atitle><jtitle>European journal of clinical pharmacology</jtitle><stitle>Eur J Clin Pharmacol</stitle><addtitle>Eur J Clin Pharmacol</addtitle><date>2009-07-01</date><risdate>2009</risdate><volume>65</volume><issue>7</issue><spage>699</spage><epage>704</epage><pages>699-704</pages><issn>0031-6970</issn><eissn>1432-1041</eissn><abstract>Purpose Fluvoxamine (FVX) is metabolized by cytochrome P450 (CYP) 2D6 and CYP1A2 and inhibits CYP3A4. The aim of this study was to investigate the factors responsible for interindividual variability in the extent of interaction between FVX and alprazolam (ALP). Methods Blood samples were taken from 49 depressive patients to determine plasma concentration of FVX, ALP or both. Twenty-four samples were taken during the FVX-alone period, 21 samples during the ALP-alone period and 30 samples during the FVX-ALP period. Subjects were also genotyped for CYP2D6. Results The concentration-to-dose (C/D) ratio of ALP during the FVX-treatment period was significantly higher than that during the ALP-alone period. The CYP2D6 genotype affected neither the C/D ratios of FVX nor the extent of interaction. The mean C/D ratio of FVX in smokers was reduced by more than 30% in comparison with that in non-smokers. The mean C/D ratio of ALP in non-smokers was increased by FVX, while that in smokers was unchanged. Conclusions The extent of interaction between FVX and ALP may be affected by smoking, which alters the C/D ratio of FVX. Therefore, when FVX and ALP are concomitantly administered, it should be noted that non-smokers may exhibit greater drug interaction than smokers.</abstract><cop>Berlin/Heidelberg</cop><pub>Berlin/Heidelberg : Springer-Verlag</pub><pmid>19225771</pmid><doi>10.1007/s00228-009-0629-4</doi><tpages>6</tpages></addata></record> |
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| subjects | Adult and adolescent clinical studies Alleles Alprazolam Alprazolam - blood Alprazolam - therapeutic use Antidepressants Biological and medical sciences Biomedical and Life Sciences Biomedicine CYP2D6 Cytochrome P-450 CYP2D6 - genetics Dose-Response Relationship, Drug Drug interaction Drug Interactions - genetics Fluvoxamine Fluvoxamine - blood Fluvoxamine - therapeutic use Genotype Genotype & phenotype Humans Medical sciences Pharmacokinectics and Disposition Pharmacology Pharmacology. Drug treatments Pharmacology/Toxicology Polymorphism Polymorphism, Genetic - drug effects Psychology. Psychoanalysis. Psychiatry Psychopathology. Psychiatry Psychophysiologic Disorders - drug therapy Psychophysiologic Disorders - genetics Psychotropic drugs Serotonin Uptake Inhibitors - blood Serotonin Uptake Inhibitors - therapeutic use Smoking Smoking - metabolism Somatoform disorders. Psychosomatics Tobacco, tobacco smoking Toxicology |
| title | Effect of smoking and CYP2D6 polymorphisms on the extent of fluvoxamine-alprazolam interaction in patients with psychosomatic disease |
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