Population pharmacokinetic analysis of certolizumab pegol in patients with Crohn's disease
Certolizumab pegol (CZP), an anti–tumor necrosis factor α agent, is an effective therapy for Crohn's disease (CD). A population pharmacokinetic (PK) analysis of subcutaneously administered CZP was performed using data from 2157 CD patients from 9 separate studies. The aim was to determine which...
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| Veröffentlicht in: | Journal of clinical pharmacology 2015-08, Vol.55 (8), p.866-874 |
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| creator | Wade, Janet R. Parker, Gerry Kosutic, Gordana Feagen, Brian G. Sandborn, William J. Laveille, Christian Oliver, Ruth |
| description | Certolizumab pegol (CZP), an anti–tumor necrosis factor α agent, is an effective therapy for Crohn's disease (CD). A population pharmacokinetic (PK) analysis of subcutaneously administered CZP was performed using data from 2157 CD patients from 9 separate studies. The aim was to determine which covariates influence the disposition of CZP. The final CZP population PK model consisted of a baseline, first‐order absorption, and 1‐compartment disposition. CZP antibodies were treated as a structural model covariate and caused apparent clearance (CL/F) to increase from 0.685 to 2.74 L/day. Body surface area (BSA) influenced both CL/F and apparent volume of distribution (V/F) in a linear fashion; both parameters increased by more than 53% and 49%, respectively, across the range of BSA measurements in the data. Albumin influenced CZP CL/F in a nonlinear fashion; CL/F decreased from 1.05 to 0.613 L/day with increasing albumin concentrations in antibody‐negative patients. C‐reactive protein (CRP) had a borderline influence and CL/F increased by more than 20% across the range of CRP measurements in the data set. Race had a minor influence on V/F. The determined covariates' impact on CZP disposition may be of clinical utility in CZP therapy of CD patients when the PK/pharmacodynamic relationship becomes available. |
| doi_str_mv | 10.1002/jcph.491 |
| format | Article |
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A population pharmacokinetic (PK) analysis of subcutaneously administered CZP was performed using data from 2157 CD patients from 9 separate studies. The aim was to determine which covariates influence the disposition of CZP. The final CZP population PK model consisted of a baseline, first‐order absorption, and 1‐compartment disposition. CZP antibodies were treated as a structural model covariate and caused apparent clearance (CL/F) to increase from 0.685 to 2.74 L/day. Body surface area (BSA) influenced both CL/F and apparent volume of distribution (V/F) in a linear fashion; both parameters increased by more than 53% and 49%, respectively, across the range of BSA measurements in the data. Albumin influenced CZP CL/F in a nonlinear fashion; CL/F decreased from 1.05 to 0.613 L/day with increasing albumin concentrations in antibody‐negative patients. C‐reactive protein (CRP) had a borderline influence and CL/F increased by more than 20% across the range of CRP measurements in the data set. Race had a minor influence on V/F. The determined covariates' impact on CZP disposition may be of clinical utility in CZP therapy of CD patients when the PK/pharmacodynamic relationship becomes available.</description><identifier>ISSN: 0091-2700</identifier><identifier>EISSN: 1552-4604</identifier><identifier>DOI: 10.1002/jcph.491</identifier><identifier>PMID: 25735646</identifier><language>eng</language><publisher>England: Blackwell Publishing Ltd</publisher><subject>Adolescent ; Adult ; Aged ; Aged, 80 and over ; anti-TNF ; Body Mass Index ; Body Surface Area ; Body Weight ; Bowel disease ; C-Reactive Protein - analysis ; certolizumab pegol ; Certolizumab Pegol - immunology ; Certolizumab Pegol - pharmacokinetics ; covariates ; Crohn Disease - blood ; Crohn Disease - immunology ; Crohn Disease - metabolism ; Crohn's disease ; Female ; Humans ; Immunosuppressive Agents - immunology ; Immunosuppressive Agents - pharmacokinetics ; Male ; Middle Aged ; Models, Biological ; NONMEM ; Pharmacometric ; Pharmacometrics ; Young Adult</subject><ispartof>Journal of clinical pharmacology, 2015-08, Vol.55 (8), p.866-874</ispartof><rights>2015 The Authors. Published by Wiley Periodicals, Inc. on behalf of American College of Clinical Pharmacology</rights><rights>2015 American College of Clinical Pharmacology</rights><rights>2015 The Authors. The Journal of Clinical Pharmacology Published by Wiley Periodicals, Inc. on behalf of American College of Clinical Pharmacology.</rights><rights>2015, The American College of Clinical Pharmacology</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c5831-a09e81036f871720d18181c0b2caada92bc7a169426382dc49ca422aa2f87c033</citedby><cites>FETCH-LOGICAL-c5831-a09e81036f871720d18181c0b2caada92bc7a169426382dc49ca422aa2f87c033</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fjcph.491$$EPDF$$P50$$Gwiley$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fjcph.491$$EHTML$$P50$$Gwiley$$Hfree_for_read</linktohtml><link.rule.ids>230,314,776,780,881,1411,27901,27902,45550,45551</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25735646$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Wade, Janet R.</creatorcontrib><creatorcontrib>Parker, Gerry</creatorcontrib><creatorcontrib>Kosutic, Gordana</creatorcontrib><creatorcontrib>Feagen, Brian G.</creatorcontrib><creatorcontrib>Sandborn, William J.</creatorcontrib><creatorcontrib>Laveille, Christian</creatorcontrib><creatorcontrib>Oliver, Ruth</creatorcontrib><title>Population pharmacokinetic analysis of certolizumab pegol in patients with Crohn's disease</title><title>Journal of clinical pharmacology</title><addtitle>The Journal of Clinical Pharmacology</addtitle><description>Certolizumab pegol (CZP), an anti–tumor necrosis factor α agent, is an effective therapy for Crohn's disease (CD). A population pharmacokinetic (PK) analysis of subcutaneously administered CZP was performed using data from 2157 CD patients from 9 separate studies. The aim was to determine which covariates influence the disposition of CZP. The final CZP population PK model consisted of a baseline, first‐order absorption, and 1‐compartment disposition. CZP antibodies were treated as a structural model covariate and caused apparent clearance (CL/F) to increase from 0.685 to 2.74 L/day. Body surface area (BSA) influenced both CL/F and apparent volume of distribution (V/F) in a linear fashion; both parameters increased by more than 53% and 49%, respectively, across the range of BSA measurements in the data. Albumin influenced CZP CL/F in a nonlinear fashion; CL/F decreased from 1.05 to 0.613 L/day with increasing albumin concentrations in antibody‐negative patients. C‐reactive protein (CRP) had a borderline influence and CL/F increased by more than 20% across the range of CRP measurements in the data set. Race had a minor influence on V/F. The determined covariates' impact on CZP disposition may be of clinical utility in CZP therapy of CD patients when the PK/pharmacodynamic relationship becomes available.</description><subject>Adolescent</subject><subject>Adult</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>anti-TNF</subject><subject>Body Mass Index</subject><subject>Body Surface Area</subject><subject>Body Weight</subject><subject>Bowel disease</subject><subject>C-Reactive Protein - analysis</subject><subject>certolizumab pegol</subject><subject>Certolizumab Pegol - immunology</subject><subject>Certolizumab Pegol - pharmacokinetics</subject><subject>covariates</subject><subject>Crohn Disease - blood</subject><subject>Crohn Disease - immunology</subject><subject>Crohn Disease - metabolism</subject><subject>Crohn's disease</subject><subject>Female</subject><subject>Humans</subject><subject>Immunosuppressive Agents - immunology</subject><subject>Immunosuppressive Agents - pharmacokinetics</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Models, Biological</subject><subject>NONMEM</subject><subject>Pharmacometric</subject><subject>Pharmacometrics</subject><subject>Young Adult</subject><issn>0091-2700</issn><issn>1552-4604</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>24P</sourceid><sourceid>EIF</sourceid><recordid>eNp1kV9v0zAUxS0EYt1A4hOgSDywBzJsx3-Sl0koohtoggmBkHixbh13cevEwU4o5dPjaqUwBLoPfri_c-6RD0JPCD4jGNOXKz20Z6wi99CMcE5zJjC7j2YYVySnEuMjdBzjCmMiGCcP0RHlsuCCiRn6cu2HycFofZ8NLYQOtF_b3oxWZ9CD20YbM7_MtAmjd_bH1MEiG8yNd5lNiiQ0_RizjR3brA6-7Z_HrLHRQDSP0IMluGge798T9Gn--mN9mV-9v3hTv7rKNS8LkgOuTElwIZalJJLihpRpNF5QDdBARRdaAhEVo6IoaaNZpYFRCkCTQOOiOEHnt77DtOhMo1OgAE4NwXYQtsqDVXc3vW3Vjf-mhCgxpWUyON0bBP91MnFUnY3aOAe98VNUu-OVIALThD77C135KaR_SpSUnOOqkuy3oQ4-xmCWhzAEq11haleYSoUl9Omf4Q_gr4YS8OIW2Hg3mhDXbtqYoFoDbmz_5ZfvcevM9r931dv6-vIOb-Novh94CGslZCG5-vzuQrGaf5jP51LVxU_qGr8P</recordid><startdate>201508</startdate><enddate>201508</enddate><creator>Wade, Janet R.</creator><creator>Parker, Gerry</creator><creator>Kosutic, Gordana</creator><creator>Feagen, Brian G.</creator><creator>Sandborn, William J.</creator><creator>Laveille, Christian</creator><creator>Oliver, Ruth</creator><general>Blackwell Publishing Ltd</general><general>American College of Clinical Pharmacology</general><general>Wiley Subscription Services, Inc</general><general>John Wiley and Sons Inc</general><scope>BSCLL</scope><scope>24P</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>7QP</scope><scope>7QR</scope><scope>7T5</scope><scope>7TK</scope><scope>7TM</scope><scope>8FD</scope><scope>FR3</scope><scope>H94</scope><scope>K9.</scope><scope>NAPCQ</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>201508</creationdate><title>Population pharmacokinetic analysis of certolizumab pegol in patients with Crohn's disease</title><author>Wade, Janet R. ; Parker, Gerry ; Kosutic, Gordana ; Feagen, Brian G. ; Sandborn, William J. ; Laveille, Christian ; Oliver, Ruth</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c5831-a09e81036f871720d18181c0b2caada92bc7a169426382dc49ca422aa2f87c033</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>Adolescent</topic><topic>Adult</topic><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>anti-TNF</topic><topic>Body Mass Index</topic><topic>Body Surface Area</topic><topic>Body Weight</topic><topic>Bowel disease</topic><topic>C-Reactive Protein - analysis</topic><topic>certolizumab pegol</topic><topic>Certolizumab Pegol - immunology</topic><topic>Certolizumab Pegol - pharmacokinetics</topic><topic>covariates</topic><topic>Crohn Disease - blood</topic><topic>Crohn Disease - immunology</topic><topic>Crohn Disease - metabolism</topic><topic>Crohn's disease</topic><topic>Female</topic><topic>Humans</topic><topic>Immunosuppressive Agents - immunology</topic><topic>Immunosuppressive Agents - pharmacokinetics</topic><topic>Male</topic><topic>Middle Aged</topic><topic>Models, Biological</topic><topic>NONMEM</topic><topic>Pharmacometric</topic><topic>Pharmacometrics</topic><topic>Young Adult</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Wade, Janet R.</creatorcontrib><creatorcontrib>Parker, Gerry</creatorcontrib><creatorcontrib>Kosutic, Gordana</creatorcontrib><creatorcontrib>Feagen, Brian G.</creatorcontrib><creatorcontrib>Sandborn, William J.</creatorcontrib><creatorcontrib>Laveille, Christian</creatorcontrib><creatorcontrib>Oliver, Ruth</creatorcontrib><collection>Istex</collection><collection>Wiley Online Library Open Access</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Immunology Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Premium</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Journal of clinical pharmacology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Wade, Janet R.</au><au>Parker, Gerry</au><au>Kosutic, Gordana</au><au>Feagen, Brian G.</au><au>Sandborn, William J.</au><au>Laveille, Christian</au><au>Oliver, Ruth</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Population pharmacokinetic analysis of certolizumab pegol in patients with Crohn's disease</atitle><jtitle>Journal of clinical pharmacology</jtitle><addtitle>The Journal of Clinical Pharmacology</addtitle><date>2015-08</date><risdate>2015</risdate><volume>55</volume><issue>8</issue><spage>866</spage><epage>874</epage><pages>866-874</pages><issn>0091-2700</issn><eissn>1552-4604</eissn><abstract>Certolizumab pegol (CZP), an anti–tumor necrosis factor α agent, is an effective therapy for Crohn's disease (CD). A population pharmacokinetic (PK) analysis of subcutaneously administered CZP was performed using data from 2157 CD patients from 9 separate studies. The aim was to determine which covariates influence the disposition of CZP. The final CZP population PK model consisted of a baseline, first‐order absorption, and 1‐compartment disposition. CZP antibodies were treated as a structural model covariate and caused apparent clearance (CL/F) to increase from 0.685 to 2.74 L/day. Body surface area (BSA) influenced both CL/F and apparent volume of distribution (V/F) in a linear fashion; both parameters increased by more than 53% and 49%, respectively, across the range of BSA measurements in the data. Albumin influenced CZP CL/F in a nonlinear fashion; CL/F decreased from 1.05 to 0.613 L/day with increasing albumin concentrations in antibody‐negative patients. C‐reactive protein (CRP) had a borderline influence and CL/F increased by more than 20% across the range of CRP measurements in the data set. Race had a minor influence on V/F. The determined covariates' impact on CZP disposition may be of clinical utility in CZP therapy of CD patients when the PK/pharmacodynamic relationship becomes available.</abstract><cop>England</cop><pub>Blackwell Publishing Ltd</pub><pmid>25735646</pmid><doi>10.1002/jcph.491</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Adolescent Adult Aged Aged, 80 and over anti-TNF Body Mass Index Body Surface Area Body Weight Bowel disease C-Reactive Protein - analysis certolizumab pegol Certolizumab Pegol - immunology Certolizumab Pegol - pharmacokinetics covariates Crohn Disease - blood Crohn Disease - immunology Crohn Disease - metabolism Crohn's disease Female Humans Immunosuppressive Agents - immunology Immunosuppressive Agents - pharmacokinetics Male Middle Aged Models, Biological NONMEM Pharmacometric Pharmacometrics Young Adult |
| title | Population pharmacokinetic analysis of certolizumab pegol in patients with Crohn's disease |
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