Interferon‐β treatment in patients with multiple sclerosis does not alter CYP2C19 or CYP2D6 activity
Aims To determine CYP2C19 and CYP2D6 activity in patients with multiple sclerosis (MS) before and during interferon (IFN)‐β treatment. Methods CYP2C19 and CYP2D6 activities were assessed using the probe drugs mephenytoin and debrisoquine, respectively. Urinary mephenytoin (S/R) and debrisoquine (d...
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| Veröffentlicht in: | British journal of clinical pharmacology 2003-09, Vol.56 (3), p.337-340 |
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| creator | Hellman, Karin Roos, Ewa Österlund, Anna Wahlberg, Anneli Gustafsson, Lars L. Bertilsson, Leif Fredrikson, Sten |
| description | Aims To determine CYP2C19 and CYP2D6 activity in patients with multiple sclerosis (MS) before and during interferon (IFN)‐β treatment.
Methods CYP2C19 and CYP2D6 activities were assessed using the probe drugs mephenytoin and debrisoquine, respectively. Urinary mephenytoin (S/R) and debrisoquine (debrisoquine/hydroxy‐debrisoquine) metabolic ratios (MR) were determined in 10 otherwise healthy Caucasian multiple sclerosis (MS) patients in the initial stage of the disease, prior to and 1 month after commencing treatment with IFN‐β (Avonex, Rebif or Betaferon). In addition, CYP2C19*2, CYP2C19*3, CYP2D6*3, CYP2D6*4, and CYP2D6*5 genotyping was performed.
Results There was no significant difference in the (S)/(R) mephenytoin ratio (mean difference 0.04; 95% CI −0.03, 0.11) or the debrisoquine MR (mean difference 0.29; 95% CI −0.44, 1.02) before and during regular IFN‐β treatment in extensive metabolizers (EM) (P = 0.5 and P = 0.4 for the respective probe drugs; n = 9 subjects). There were also no differences between the different IFN‐β treatments (P = 0.6 for the (S)/(R) mephenytoin ratio and P = 0.7 for the debrisoquine MR; anova; n = 10).
Conclusions IFN‐β treatment did not affect the activity of CYP2C19 or CYP2D6. The results suggest that it is safe to administer CYP2C19 or CYP2D6 substrates, without dose adjustment, to patients treated with IFN‐β. |
| doi_str_mv | 10.1046/j.0306-5251.2003.01859.x |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_swepu</sourceid><recordid>TN_cdi_swepub_primary_oai_swepub_ki_se_588789</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>73562558</sourcerecordid><originalsourceid>FETCH-LOGICAL-c5389-9631abd7f48243b023fc2ae39285ae2146ba76bd7592df9465d583f7b268c3a93</originalsourceid><addsrcrecordid>eNqNkc1u1DAUhS0EotOBV0DewC7BP7FjL0Ci4a9SJbqABSvLcZzWg5MMsafT2fUReBYehIfgSXBI1NIdKx_5fuf6Xh8AIEY5RgV_uckRRTxjhOGcIERzhAWT-fUDsMKUs4xgwh6C1S10BI5D2CCEKebsMTjCRGKZLCtwcdpHO7Z2HPrfNz9-_YRxtDp2to_Q9XCro0sywL2Ll7Db-ei23sJgfDIEF2Az2AD7IULtUxtYfT0nFZZwmOVbDrWJ7srFwxPwqNU-2KfLuQZf3r_7XH3Mzj59OK3enGWGUSEzySnWdVO2hSAFrRGhrSHaUkkE05bggte65AlgkjStLDhrmKBtWRMuDNWSrkE29w17u93Vaju6To8HNWinlqtvSVnFhCjFxL-e-VTpbGPStqP292z3K727VBfDlcJCFJTR1ODF0mAcvu9siKpzwVjvdW-HXVAlZZywNOQaiBk06evCaNvbRzBSU6pqo6bA1BSYmlJVf1NV18n67N8h74xLjAl4vgA6GO3bUffGhTuOIcYImbZ9NXN75-3hvwdQJ9X5pOgf6TrAqA</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>73562558</pqid></control><display><type>article</type><title>Interferon‐β treatment in patients with multiple sclerosis does not alter CYP2C19 or CYP2D6 activity</title><source>MEDLINE</source><source>Wiley Online Library Journals Frontfile Complete</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><source>SWEPUB Freely available online</source><source>Wiley Free Content</source><source>Alma/SFX Local Collection</source><creator>Hellman, Karin ; Roos, Ewa ; Österlund, Anna ; Wahlberg, Anneli ; Gustafsson, Lars L. ; Bertilsson, Leif ; Fredrikson, Sten</creator><creatorcontrib>Hellman, Karin ; Roos, Ewa ; Österlund, Anna ; Wahlberg, Anneli ; Gustafsson, Lars L. ; Bertilsson, Leif ; Fredrikson, Sten</creatorcontrib><description>Aims To determine CYP2C19 and CYP2D6 activity in patients with multiple sclerosis (MS) before and during interferon (IFN)‐β treatment.
Methods CYP2C19 and CYP2D6 activities were assessed using the probe drugs mephenytoin and debrisoquine, respectively. Urinary mephenytoin (S/R) and debrisoquine (debrisoquine/hydroxy‐debrisoquine) metabolic ratios (MR) were determined in 10 otherwise healthy Caucasian multiple sclerosis (MS) patients in the initial stage of the disease, prior to and 1 month after commencing treatment with IFN‐β (Avonex, Rebif or Betaferon). In addition, CYP2C19*2, CYP2C19*3, CYP2D6*3, CYP2D6*4, and CYP2D6*5 genotyping was performed.
Results There was no significant difference in the (S)/(R) mephenytoin ratio (mean difference 0.04; 95% CI −0.03, 0.11) or the debrisoquine MR (mean difference 0.29; 95% CI −0.44, 1.02) before and during regular IFN‐β treatment in extensive metabolizers (EM) (P = 0.5 and P = 0.4 for the respective probe drugs; n = 9 subjects). There were also no differences between the different IFN‐β treatments (P = 0.6 for the (S)/(R) mephenytoin ratio and P = 0.7 for the debrisoquine MR; anova; n = 10).
Conclusions IFN‐β treatment did not affect the activity of CYP2C19 or CYP2D6. The results suggest that it is safe to administer CYP2C19 or CYP2D6 substrates, without dose adjustment, to patients treated with IFN‐β.</description><identifier>ISSN: 0306-5251</identifier><identifier>EISSN: 1365-2125</identifier><identifier>DOI: 10.1046/j.0306-5251.2003.01859.x</identifier><identifier>PMID: 12919185</identifier><identifier>CODEN: BCPHBM</identifier><language>eng</language><publisher>Oxford, UK: Blackwell Science Ltd</publisher><subject>Adult ; Aryl Hydrocarbon Hydroxylases - genetics ; Aryl Hydrocarbon Hydroxylases - metabolism ; Biological and medical sciences ; CYP2C19 ; CYP2D6 ; Cytochrome P-450 CYP2C19 ; Cytochrome P-450 CYP2D6 - genetics ; Cytochrome P-450 CYP2D6 - metabolism ; cytochrome P‐450 ; Female ; Genotype ; Humans ; Immunomodulators ; Interferon-beta - therapeutic use ; interferon‐β ; Male ; Medical sciences ; Middle Aged ; Mixed Function Oxygenases - genetics ; Mixed Function Oxygenases - metabolism ; multiple sclerosis ; Multiple Sclerosis - drug therapy ; Multiple Sclerosis - metabolism ; Pharmacology. Drug treatments ; Phenotype ; Short Reports</subject><ispartof>British journal of clinical pharmacology, 2003-09, Vol.56 (3), p.337-340</ispartof><rights>2004 INIST-CNRS</rights><rights>2003 Blackwell Publishing Ltd 2003</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c5389-9631abd7f48243b023fc2ae39285ae2146ba76bd7592df9465d583f7b268c3a93</citedby><cites>FETCH-LOGICAL-c5389-9631abd7f48243b023fc2ae39285ae2146ba76bd7592df9465d583f7b268c3a93</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1046%2Fj.0306-5251.2003.01859.x$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1046%2Fj.0306-5251.2003.01859.x$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>230,314,551,777,781,882,1412,1428,27905,27906,45555,45556,46390,46814</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=15055229$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/12919185$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttp://kipublications.ki.se/Default.aspx?queryparsed=id:1930815$$DView record from Swedish Publication Index$$Hfree_for_read</backlink></links><search><creatorcontrib>Hellman, Karin</creatorcontrib><creatorcontrib>Roos, Ewa</creatorcontrib><creatorcontrib>Österlund, Anna</creatorcontrib><creatorcontrib>Wahlberg, Anneli</creatorcontrib><creatorcontrib>Gustafsson, Lars L.</creatorcontrib><creatorcontrib>Bertilsson, Leif</creatorcontrib><creatorcontrib>Fredrikson, Sten</creatorcontrib><title>Interferon‐β treatment in patients with multiple sclerosis does not alter CYP2C19 or CYP2D6 activity</title><title>British journal of clinical pharmacology</title><addtitle>Br J Clin Pharmacol</addtitle><description>Aims To determine CYP2C19 and CYP2D6 activity in patients with multiple sclerosis (MS) before and during interferon (IFN)‐β treatment.
Methods CYP2C19 and CYP2D6 activities were assessed using the probe drugs mephenytoin and debrisoquine, respectively. Urinary mephenytoin (S/R) and debrisoquine (debrisoquine/hydroxy‐debrisoquine) metabolic ratios (MR) were determined in 10 otherwise healthy Caucasian multiple sclerosis (MS) patients in the initial stage of the disease, prior to and 1 month after commencing treatment with IFN‐β (Avonex, Rebif or Betaferon). In addition, CYP2C19*2, CYP2C19*3, CYP2D6*3, CYP2D6*4, and CYP2D6*5 genotyping was performed.
Results There was no significant difference in the (S)/(R) mephenytoin ratio (mean difference 0.04; 95% CI −0.03, 0.11) or the debrisoquine MR (mean difference 0.29; 95% CI −0.44, 1.02) before and during regular IFN‐β treatment in extensive metabolizers (EM) (P = 0.5 and P = 0.4 for the respective probe drugs; n = 9 subjects). There were also no differences between the different IFN‐β treatments (P = 0.6 for the (S)/(R) mephenytoin ratio and P = 0.7 for the debrisoquine MR; anova; n = 10).
Conclusions IFN‐β treatment did not affect the activity of CYP2C19 or CYP2D6. The results suggest that it is safe to administer CYP2C19 or CYP2D6 substrates, without dose adjustment, to patients treated with IFN‐β.</description><subject>Adult</subject><subject>Aryl Hydrocarbon Hydroxylases - genetics</subject><subject>Aryl Hydrocarbon Hydroxylases - metabolism</subject><subject>Biological and medical sciences</subject><subject>CYP2C19</subject><subject>CYP2D6</subject><subject>Cytochrome P-450 CYP2C19</subject><subject>Cytochrome P-450 CYP2D6 - genetics</subject><subject>Cytochrome P-450 CYP2D6 - metabolism</subject><subject>cytochrome P‐450</subject><subject>Female</subject><subject>Genotype</subject><subject>Humans</subject><subject>Immunomodulators</subject><subject>Interferon-beta - therapeutic use</subject><subject>interferon‐β</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Middle Aged</subject><subject>Mixed Function Oxygenases - genetics</subject><subject>Mixed Function Oxygenases - metabolism</subject><subject>multiple sclerosis</subject><subject>Multiple Sclerosis - drug therapy</subject><subject>Multiple Sclerosis - metabolism</subject><subject>Pharmacology. Drug treatments</subject><subject>Phenotype</subject><subject>Short Reports</subject><issn>0306-5251</issn><issn>1365-2125</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2003</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>D8T</sourceid><recordid>eNqNkc1u1DAUhS0EotOBV0DewC7BP7FjL0Ci4a9SJbqABSvLcZzWg5MMsafT2fUReBYehIfgSXBI1NIdKx_5fuf6Xh8AIEY5RgV_uckRRTxjhOGcIERzhAWT-fUDsMKUs4xgwh6C1S10BI5D2CCEKebsMTjCRGKZLCtwcdpHO7Z2HPrfNz9-_YRxtDp2to_Q9XCro0sywL2Ll7Db-ei23sJgfDIEF2Az2AD7IULtUxtYfT0nFZZwmOVbDrWJ7srFwxPwqNU-2KfLuQZf3r_7XH3Mzj59OK3enGWGUSEzySnWdVO2hSAFrRGhrSHaUkkE05bggte65AlgkjStLDhrmKBtWRMuDNWSrkE29w17u93Vaju6To8HNWinlqtvSVnFhCjFxL-e-VTpbGPStqP292z3K727VBfDlcJCFJTR1ODF0mAcvu9siKpzwVjvdW-HXVAlZZywNOQaiBk06evCaNvbRzBSU6pqo6bA1BSYmlJVf1NV18n67N8h74xLjAl4vgA6GO3bUffGhTuOIcYImbZ9NXN75-3hvwdQJ9X5pOgf6TrAqA</recordid><startdate>200309</startdate><enddate>200309</enddate><creator>Hellman, Karin</creator><creator>Roos, Ewa</creator><creator>Österlund, Anna</creator><creator>Wahlberg, Anneli</creator><creator>Gustafsson, Lars L.</creator><creator>Bertilsson, Leif</creator><creator>Fredrikson, Sten</creator><general>Blackwell Science Ltd</general><general>Blackwell Science</general><general>Blackwell Science Inc</general><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>7X8</scope><scope>5PM</scope><scope>ADTPV</scope><scope>AOWAS</scope><scope>D8T</scope><scope>ZZAVC</scope></search><sort><creationdate>200309</creationdate><title>Interferon‐β treatment in patients with multiple sclerosis does not alter CYP2C19 or CYP2D6 activity</title><author>Hellman, Karin ; Roos, Ewa ; Österlund, Anna ; Wahlberg, Anneli ; Gustafsson, Lars L. ; Bertilsson, Leif ; Fredrikson, Sten</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c5389-9631abd7f48243b023fc2ae39285ae2146ba76bd7592df9465d583f7b268c3a93</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2003</creationdate><topic>Adult</topic><topic>Aryl Hydrocarbon Hydroxylases - genetics</topic><topic>Aryl Hydrocarbon Hydroxylases - metabolism</topic><topic>Biological and medical sciences</topic><topic>CYP2C19</topic><topic>CYP2D6</topic><topic>Cytochrome P-450 CYP2C19</topic><topic>Cytochrome P-450 CYP2D6 - genetics</topic><topic>Cytochrome P-450 CYP2D6 - metabolism</topic><topic>cytochrome P‐450</topic><topic>Female</topic><topic>Genotype</topic><topic>Humans</topic><topic>Immunomodulators</topic><topic>Interferon-beta - therapeutic use</topic><topic>interferon‐β</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Middle Aged</topic><topic>Mixed Function Oxygenases - genetics</topic><topic>Mixed Function Oxygenases - metabolism</topic><topic>multiple sclerosis</topic><topic>Multiple Sclerosis - drug therapy</topic><topic>Multiple Sclerosis - metabolism</topic><topic>Pharmacology. Drug treatments</topic><topic>Phenotype</topic><topic>Short Reports</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Hellman, Karin</creatorcontrib><creatorcontrib>Roos, Ewa</creatorcontrib><creatorcontrib>Österlund, Anna</creatorcontrib><creatorcontrib>Wahlberg, Anneli</creatorcontrib><creatorcontrib>Gustafsson, Lars L.</creatorcontrib><creatorcontrib>Bertilsson, Leif</creatorcontrib><creatorcontrib>Fredrikson, Sten</creatorcontrib><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>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>SwePub</collection><collection>SwePub Articles</collection><collection>SWEPUB Freely available online</collection><collection>SwePub Articles full text</collection><jtitle>British journal of clinical pharmacology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Hellman, Karin</au><au>Roos, Ewa</au><au>Österlund, Anna</au><au>Wahlberg, Anneli</au><au>Gustafsson, Lars L.</au><au>Bertilsson, Leif</au><au>Fredrikson, Sten</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Interferon‐β treatment in patients with multiple sclerosis does not alter CYP2C19 or CYP2D6 activity</atitle><jtitle>British journal of clinical pharmacology</jtitle><addtitle>Br J Clin Pharmacol</addtitle><date>2003-09</date><risdate>2003</risdate><volume>56</volume><issue>3</issue><spage>337</spage><epage>340</epage><pages>337-340</pages><issn>0306-5251</issn><eissn>1365-2125</eissn><coden>BCPHBM</coden><abstract>Aims To determine CYP2C19 and CYP2D6 activity in patients with multiple sclerosis (MS) before and during interferon (IFN)‐β treatment.
Methods CYP2C19 and CYP2D6 activities were assessed using the probe drugs mephenytoin and debrisoquine, respectively. Urinary mephenytoin (S/R) and debrisoquine (debrisoquine/hydroxy‐debrisoquine) metabolic ratios (MR) were determined in 10 otherwise healthy Caucasian multiple sclerosis (MS) patients in the initial stage of the disease, prior to and 1 month after commencing treatment with IFN‐β (Avonex, Rebif or Betaferon). In addition, CYP2C19*2, CYP2C19*3, CYP2D6*3, CYP2D6*4, and CYP2D6*5 genotyping was performed.
Results There was no significant difference in the (S)/(R) mephenytoin ratio (mean difference 0.04; 95% CI −0.03, 0.11) or the debrisoquine MR (mean difference 0.29; 95% CI −0.44, 1.02) before and during regular IFN‐β treatment in extensive metabolizers (EM) (P = 0.5 and P = 0.4 for the respective probe drugs; n = 9 subjects). There were also no differences between the different IFN‐β treatments (P = 0.6 for the (S)/(R) mephenytoin ratio and P = 0.7 for the debrisoquine MR; anova; n = 10).
Conclusions IFN‐β treatment did not affect the activity of CYP2C19 or CYP2D6. The results suggest that it is safe to administer CYP2C19 or CYP2D6 substrates, without dose adjustment, to patients treated with IFN‐β.</abstract><cop>Oxford, UK</cop><pub>Blackwell Science Ltd</pub><pmid>12919185</pmid><doi>10.1046/j.0306-5251.2003.01859.x</doi><tpages>4</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Adult Aryl Hydrocarbon Hydroxylases - genetics Aryl Hydrocarbon Hydroxylases - metabolism Biological and medical sciences CYP2C19 CYP2D6 Cytochrome P-450 CYP2C19 Cytochrome P-450 CYP2D6 - genetics Cytochrome P-450 CYP2D6 - metabolism cytochrome P‐450 Female Genotype Humans Immunomodulators Interferon-beta - therapeutic use interferon‐β Male Medical sciences Middle Aged Mixed Function Oxygenases - genetics Mixed Function Oxygenases - metabolism multiple sclerosis Multiple Sclerosis - drug therapy Multiple Sclerosis - metabolism Pharmacology. Drug treatments Phenotype Short Reports |
| title | Interferon‐β treatment in patients with multiple sclerosis does not alter CYP2C19 or CYP2D6 activity |
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