Influence of methotrexate on infliximab pharmacokinetics and pharmacodynamics in ankylosing spondylitis
Identifieur interne : 000427 ( Pmc/Curation ); précédent : 000426; suivant : 000428Influence of methotrexate on infliximab pharmacokinetics and pharmacodynamics in ankylosing spondylitis
Auteurs : David Ternant ; Denis Mulleman ; Francine Lauféron ; Céline Vignault ; Emilie Ducourau ; Daniel Wendling ; Philippe Goupille [France] ; Gilles PaintaudSource :
- British Journal of Clinical Pharmacology [ 0306-5251 ] ; 2012.
Abstract
Infliximab, an anti-tumour necrosis factor α monoclonal antibody, has profoundly modified the treatment of several inflammatory diseases. The objective was to assess the influence of methotrexate on the variability of infliximab pharmacokinetics and concentration–effect relationship in axial ankylosing spondylitis (AAS) patients.
Twenty-six patients with AAS were included in a prospective study. They were treated by infliximab 5 mg kg−1 infusions at weeks 0, 2, 6, 12 and 18. Infliximab concentrations were measured before, and 2 and 4 h after each infusion, and at each intermediate visit (weeks 1, 3, 4, 5, 8, 10 and 14). Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) was measured at each visit. Infliximab pharmacokinetics was described using a two-compartment model with first-order distribution and elimination constants. A population approach was used. Infliximab pharmacodynamics was described using the area under the BASDAI curve.
A total of 507 blood samples and 329 BASDAI measurements were collected. The following pharmacokinetic parameters were obtained (interindividual coefficient of variation): volumes of distribution for the central compartment = 2.4 l (9.6%) and peripheral compartment = 1.8 l (26%), systemic clearance = 0.23 l day−1 (22%) and intercompartment clearance = 2.3 l day−1. Methotrexate influenced neither pharmacokinetic nor BASDAI variability.
Using the present dosage, the clinical efficacy of infliximab is only weakly influenced by its serum concentrations. The results do not support the combination of methotrexate with infliximab in ankylosing spondylitis.
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DOI: 10.1111/j.1365-2125.2011.04050.x
PubMed: 21692827
PubMed Central: 3248256
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type="wicri:source">PMC</idno><idno type="pmid">21692827</idno><idno type="pmc">3248256</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3248256</idno><idno type="RBID">PMC:3248256</idno><idno type="doi">10.1111/j.1365-2125.2011.04050.x</idno><date when="2012">2012</date><idno type="wicri:Area/Pmc/Corpus">000430</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000430</idno><idno type="wicri:Area/Pmc/Curation">000427</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">000427</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Influence of methotrexate on infliximab pharmacokinetics and pharmacodynamics in ankylosing spondylitis</title><author><name sortKey="Ternant, David" sort="Ternant, David" uniqKey="Ternant D" first="David" last="Ternant">David Ternant</name><affiliation><nlm:aff id="au1"><institution>Université François Rabelais de Tours</institution><addr-line>Tours</addr-line></nlm:aff></affiliation><affiliation><nlm:aff id="au2"><institution>CNRS, UMR 6239, ‘Genetics, Immunotherapy, Chemistry and Cancer’</institution><addr-line>Tours</addr-line></nlm:aff></affiliation><affiliation><nlm:aff id="au3"><institution>CHRU de Tours, Laboratory of Pharmacology-Toxicology</institution><addr-line>Tours</addr-line></nlm:aff></affiliation></author><author><name sortKey="Mulleman, Denis" sort="Mulleman, Denis" uniqKey="Mulleman D" first="Denis" last="Mulleman">Denis Mulleman</name><affiliation><nlm:aff id="au1"><institution>Université François Rabelais de Tours</institution><addr-line>Tours</addr-line></nlm:aff></affiliation><affiliation><nlm:aff id="au2"><institution>CNRS, UMR 6239, ‘Genetics, Immunotherapy, Chemistry and Cancer’</institution><addr-line>Tours</addr-line></nlm:aff></affiliation><affiliation><nlm:aff id="au4"><institution>CHRU de Tours, Department of Rheumatology</institution><addr-line>Tours</addr-line></nlm:aff></affiliation></author><author><name sortKey="Lauferon, Francine" sort="Lauferon, Francine" uniqKey="Lauferon F" first="Francine" last="Lauféron">Francine Lauféron</name><affiliation><nlm:aff id="au1"><institution>Université François Rabelais de Tours</institution><addr-line>Tours</addr-line></nlm:aff></affiliation><affiliation><nlm:aff id="au4"><institution>CHRU de Tours, Department of Rheumatology</institution><addr-line>Tours</addr-line></nlm:aff></affiliation></author><author><name sortKey="Vignault, Celine" sort="Vignault, Celine" uniqKey="Vignault C" first="Céline" last="Vignault">Céline Vignault</name><affiliation><nlm:aff id="au1"><institution>Université François Rabelais de Tours</institution><addr-line>Tours</addr-line></nlm:aff></affiliation><affiliation><nlm:aff id="au2"><institution>CNRS, UMR 6239, ‘Genetics, Immunotherapy, Chemistry and Cancer’</institution><addr-line>Tours</addr-line></nlm:aff></affiliation><affiliation><nlm:aff id="au3"><institution>CHRU de Tours, Laboratory of Pharmacology-Toxicology</institution><addr-line>Tours</addr-line></nlm:aff></affiliation></author><author><name sortKey="Ducourau, Emilie" sort="Ducourau, Emilie" uniqKey="Ducourau E" first="Emilie" last="Ducourau">Emilie Ducourau</name><affiliation><nlm:aff id="au1"><institution>Université François Rabelais de Tours</institution><addr-line>Tours</addr-line></nlm:aff></affiliation><affiliation><nlm:aff id="au2"><institution>CNRS, UMR 6239, ‘Genetics, Immunotherapy, Chemistry and Cancer’</institution><addr-line>Tours</addr-line></nlm:aff></affiliation><affiliation><nlm:aff id="au4"><institution>CHRU de Tours, Department of Rheumatology</institution><addr-line>Tours</addr-line></nlm:aff></affiliation></author><author><name sortKey="Wendling, Daniel" sort="Wendling, Daniel" uniqKey="Wendling D" first="Daniel" last="Wendling">Daniel Wendling</name><affiliation><nlm:aff id="au5"><institution>CHRU de Besançon, Department of Rheumatology</institution><addr-line>Besançon</addr-line></nlm:aff></affiliation></author><author><name sortKey="Goupille, Philippe" sort="Goupille, Philippe" uniqKey="Goupille P" first="Philippe" last="Goupille">Philippe Goupille</name><affiliation><nlm:aff id="au1"><institution>Université François Rabelais de Tours</institution><addr-line>Tours</addr-line></nlm:aff></affiliation><affiliation><nlm:aff id="au2"><institution>CNRS, UMR 6239, ‘Genetics, Immunotherapy, Chemistry and Cancer’</institution><addr-line>Tours</addr-line></nlm:aff></affiliation><affiliation><nlm:aff id="au4"><institution>CHRU de Tours, Department of Rheumatology</institution><addr-line>Tours</addr-line></nlm:aff></affiliation><affiliation wicri:level="1"><nlm:aff id="au6"><institution>INSERM CIC 202</institution><addr-line>Tours, France</addr-line></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Tours</wicri:regionArea></affiliation></author><author><name sortKey="Paintaud, Gilles" sort="Paintaud, Gilles" uniqKey="Paintaud G" first="Gilles" last="Paintaud">Gilles Paintaud</name><affiliation><nlm:aff id="au1"><institution>Université François Rabelais de Tours</institution><addr-line>Tours</addr-line></nlm:aff></affiliation><affiliation><nlm:aff id="au2"><institution>CNRS, UMR 6239, ‘Genetics, Immunotherapy, Chemistry and Cancer’</institution><addr-line>Tours</addr-line></nlm:aff></affiliation><affiliation><nlm:aff id="au3"><institution>CHRU de Tours, Laboratory of Pharmacology-Toxicology</institution><addr-line>Tours</addr-line></nlm:aff></affiliation></author></analytic><series><title level="j">British Journal of Clinical Pharmacology</title><idno type="ISSN">0306-5251</idno><idno type="eISSN">1365-2125</idno><imprint><date when="2012">2012</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><sec><title>AIMS</title><p>Infliximab, an anti-tumour necrosis factor α monoclonal antibody, has profoundly modified the treatment of several inflammatory diseases. The objective was to assess the influence of methotrexate on the variability of infliximab pharmacokinetics and concentration–effect relationship in axial ankylosing spondylitis (AAS) patients.</p></sec><sec><title>METHODS</title><p>Twenty-six patients with AAS were included in a prospective study. They were treated by infliximab 5 mg kg<sup>−1</sup> infusions at weeks 0, 2, 6, 12 and 18. Infliximab concentrations were measured before, and 2 and 4 h after each infusion, and at each intermediate visit (weeks 1, 3, 4, 5, 8, 10 and 14). Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) was measured at each visit. Infliximab pharmacokinetics was described using a two-compartment model with first-order distribution and elimination constants. A population approach was used. Infliximab pharmacodynamics was described using the area under the BASDAI curve.</p></sec><sec><title>RESULTS</title><p>A total of 507 blood samples and 329 BASDAI measurements were collected. The following pharmacokinetic parameters were obtained (interindividual coefficient of variation): volumes of distribution for the central compartment = 2.4 l (9.6%) and peripheral compartment = 1.8 l (26%), systemic clearance = 0.23 l day<sup>−1</sup> (22%) and intercompartment clearance = 2.3 l day<sup>−1</sup>. Methotrexate influenced neither pharmacokinetic nor BASDAI variability.</p></sec><sec><title>CONCLUSIONS</title><p>Using the present dosage, the clinical efficacy of infliximab is only weakly influenced by its serum concentrations. The results do not support the combination of methotrexate with infliximab in ankylosing spondylitis.</p></sec></div></front></TEI><pmc article-type="research-article"><pmc-comment>The publisher of this article does not allow downloading of the full text in XML form.</pmc-comment>
<front><journal-meta><journal-id journal-id-type="nlm-ta">Br J Clin Pharmacol</journal-id><journal-id journal-id-type="publisher-id">bcp</journal-id><journal-title-group><journal-title>British Journal of Clinical Pharmacology</journal-title></journal-title-group><issn pub-type="ppub">0306-5251</issn><issn pub-type="epub">1365-2125</issn><publisher><publisher-name>Blackwell Science Inc</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">21692827</article-id><article-id pub-id-type="pmc">3248256</article-id><article-id pub-id-type="doi">10.1111/j.1365-2125.2011.04050.x</article-id><article-categories><subj-group subj-group-type="heading"><subject>Pharmacokinetics</subject></subj-group></article-categories><title-group><article-title>Influence of methotrexate on infliximab pharmacokinetics and pharmacodynamics in ankylosing spondylitis</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Ternant</surname><given-names>David</given-names></name><xref ref-type="aff" rid="au1">1</xref><xref ref-type="aff" rid="au2">2</xref><xref ref-type="aff" rid="au3">3</xref></contrib><contrib contrib-type="author"><name><surname>Mulleman</surname><given-names>Denis</given-names></name><xref ref-type="aff" rid="au1">1</xref><xref ref-type="aff" rid="au2">2</xref><xref ref-type="aff" rid="au4">4</xref></contrib><contrib contrib-type="author"><name><surname>Lauféron</surname><given-names>Francine</given-names></name><xref ref-type="aff" rid="au1">1</xref><xref ref-type="aff" rid="au4">4</xref></contrib><contrib contrib-type="author"><name><surname>Vignault</surname><given-names>Céline</given-names></name><xref ref-type="aff" rid="au1">1</xref><xref ref-type="aff" rid="au2">2</xref><xref ref-type="aff" rid="au3">3</xref></contrib><contrib contrib-type="author"><name><surname>Ducourau</surname><given-names>Emilie</given-names></name><xref ref-type="aff" rid="au1">1</xref><xref ref-type="aff" rid="au2">2</xref><xref ref-type="aff" rid="au4">4</xref></contrib><contrib contrib-type="author"><name><surname>Wendling</surname><given-names>Daniel</given-names></name><xref ref-type="aff" rid="au5">5</xref></contrib><contrib contrib-type="author"><name><surname>Goupille</surname><given-names>Philippe</given-names></name><xref ref-type="aff" rid="au1">1</xref><xref ref-type="aff" rid="au2">2</xref><xref ref-type="aff" rid="au4">4</xref><xref ref-type="aff" rid="au6">6</xref></contrib><contrib contrib-type="author"><name><surname>Paintaud</surname><given-names>Gilles</given-names></name><xref ref-type="aff" rid="au1">1</xref><xref ref-type="aff" rid="au2">2</xref><xref ref-type="aff" rid="au3">3</xref></contrib><aff id="au1"><label>1</label><institution>Université François Rabelais de Tours</institution><addr-line>Tours</addr-line></aff><aff id="au2"><label>2</label><institution>CNRS, UMR 6239, ‘Genetics, Immunotherapy, Chemistry and Cancer’</institution><addr-line>Tours</addr-line></aff><aff id="au3"><label>3</label><institution>CHRU de Tours, Laboratory of Pharmacology-Toxicology</institution><addr-line>Tours</addr-line></aff><aff id="au4"><label>4</label><institution>CHRU de Tours, Department of Rheumatology</institution><addr-line>Tours</addr-line></aff><aff id="au5"><label>5</label><institution>CHRU de Besançon, Department of Rheumatology</institution><addr-line>Besançon</addr-line></aff><aff id="au6"><label>6</label><institution>INSERM CIC 202</institution><addr-line>Tours, France</addr-line></aff></contrib-group><author-notes><corresp id="cor1">Dr David Ternant, Université François Rabelais de Tours, 2 boulevard Tonnelle, Tours 37044, France. Tel.: +33 2 4747 6008. Fax: +33 2 4747 6011. E-mail: <email>david.ternant@free.fr</email></corresp><fn><p>D.T. and D.M. contributed equally to this work.</p></fn></author-notes><pub-date pub-type="ppub"><month>1</month><year>2012</year></pub-date><volume>73</volume><issue>1</issue><fpage>55</fpage><lpage>65</lpage><history><date date-type="received"><day>08</day><month>10</month><year>2010</year></date><date date-type="accepted"><day>10</day><month>6</month><year>2011</year></date><date date-type="accepted"><day>22</day><month>6</month><year>2011</year></date></history><permissions><copyright-statement>Copyright © 2012 The British Pharmacological Society</copyright-statement><copyright-year>2012</copyright-year></permissions><abstract><sec><title>AIMS</title><p>Infliximab, an anti-tumour necrosis factor α monoclonal antibody, has profoundly modified the treatment of several inflammatory diseases. The objective was to assess the influence of methotrexate on the variability of infliximab pharmacokinetics and concentration–effect relationship in axial ankylosing spondylitis (AAS) patients.</p></sec><sec><title>METHODS</title><p>Twenty-six patients with AAS were included in a prospective study. They were treated by infliximab 5 mg kg<sup>−1</sup> infusions at weeks 0, 2, 6, 12 and 18. Infliximab concentrations were measured before, and 2 and 4 h after each infusion, and at each intermediate visit (weeks 1, 3, 4, 5, 8, 10 and 14). Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) was measured at each visit. Infliximab pharmacokinetics was described using a two-compartment model with first-order distribution and elimination constants. A population approach was used. Infliximab pharmacodynamics was described using the area under the BASDAI curve.</p></sec><sec><title>RESULTS</title><p>A total of 507 blood samples and 329 BASDAI measurements were collected. The following pharmacokinetic parameters were obtained (interindividual coefficient of variation): volumes of distribution for the central compartment = 2.4 l (9.6%) and peripheral compartment = 1.8 l (26%), systemic clearance = 0.23 l day<sup>−1</sup> (22%) and intercompartment clearance = 2.3 l day<sup>−1</sup>. Methotrexate influenced neither pharmacokinetic nor BASDAI variability.</p></sec><sec><title>CONCLUSIONS</title><p>Using the present dosage, the clinical efficacy of infliximab is only weakly influenced by its serum concentrations. The results do not support the combination of methotrexate with infliximab in ankylosing spondylitis.</p></sec></abstract><kwd-group><kwd>ankylosing spondylitis</kwd><kwd>infliximab</kwd><kwd>methotrexate</kwd><kwd>pharmacokinetics</kwd></kwd-group></article-meta></front></pmc></record>Pour manipuler ce document sous Unix (Dilib)
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