Pharmacokinetics and Metabolism of Ziritaxestat (GLPG1690) in Healthy Male Volunteers Following Intravenous and Oral Administration
Ziritaxestat is a novel inhibitor of autotaxin, an enzyme responsible for the production of lysophosphatidic acid, the downstream signaling of which mediates responses to tissue injury and has been implicated in the pathogenesis of fibrotic conditions such as idiopathic pulmonary fibrosis and system...
Saved in:
| Published in | Clinical pharmacology in drug development Vol. 11; no. 2; pp. 246 - 256 |
|---|---|
| Main Authors | , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
United States
Wiley Subscription Services, Inc
01.02.2022
John Wiley and Sons Inc |
| Subjects | |
| Online Access | Get full text |
Cover
Loading…
| Abstract | Ziritaxestat is a novel inhibitor of autotaxin, an enzyme responsible for the production of lysophosphatidic acid, the downstream signaling of which mediates responses to tissue injury and has been implicated in the pathogenesis of fibrotic conditions such as idiopathic pulmonary fibrosis and systemic sclerosis. This study (Clinical Trial Registration: NCT03787186) was designed to assess the absorption, distribution, metabolism, and excretion of orally administered 600‐mg ziritaxestat labeled with a carbon‐14 tracer (14C‐ziritaxestat). To understand the absolute bioavailability of ziritaxestat, an intravenous 100‐μg microdose, labeled with a microtracer amount of 14C radiation, was administered in a separate part of the study, following an unlabeled 600‐mg therapeutic oral dose of ziritaxestat. Six healthy male subjects completed each study part. The majority of the labeled oral dose was recovered in feces (77%), with a total mass balance of 84%. The absolute bioavailability of ziritaxestat was 54%. Ziritaxestat was the main (76%) circulating drug‐related product. There were 7 treatment‐emergent adverse events, all of which were considered mild and not considered to be related to the study drug. |
|---|---|
| AbstractList | Ziritaxestat is a novel inhibitor of autotaxin, an enzyme responsible for the production of lysophosphatidic acid, the downstream signaling of which mediates responses to tissue injury and has been implicated in the pathogenesis of fibrotic conditions such as idiopathic pulmonary fibrosis and systemic sclerosis. This study (Clinical Trial Registration: NCT03787186) was designed to assess the absorption, distribution, metabolism, and excretion of orally administered 600‐mg ziritaxestat labeled with a carbon‐14 tracer (
14
C‐ziritaxestat). To understand the absolute bioavailability of ziritaxestat, an intravenous 100‐μg microdose, labeled with a microtracer amount of
14
C radiation, was administered in a separate part of the study, following an unlabeled 600‐mg therapeutic oral dose of ziritaxestat. Six healthy male subjects completed each study part. The majority of the labeled oral dose was recovered in feces (77%), with a total mass balance of 84%. The absolute bioavailability of ziritaxestat was 54%. Ziritaxestat was the main (76%) circulating drug‐related product. There were 7 treatment‐emergent adverse events, all of which were considered mild and not considered to be related to the study drug. Ziritaxestat is a novel inhibitor of autotaxin, an enzyme responsible for the production of lysophosphatidic acid, the downstream signaling of which mediates responses to tissue injury and has been implicated in the pathogenesis of fibrotic conditions such as idiopathic pulmonary fibrosis and systemic sclerosis. This study (Clinical Trial Registration: NCT03787186) was designed to assess the absorption, distribution, metabolism, and excretion of orally administered 600‐mg ziritaxestat labeled with a carbon‐14 tracer (14C‐ziritaxestat). To understand the absolute bioavailability of ziritaxestat, an intravenous 100‐μg microdose, labeled with a microtracer amount of 14C radiation, was administered in a separate part of the study, following an unlabeled 600‐mg therapeutic oral dose of ziritaxestat. Six healthy male subjects completed each study part. The majority of the labeled oral dose was recovered in feces (77%), with a total mass balance of 84%. The absolute bioavailability of ziritaxestat was 54%. Ziritaxestat was the main (76%) circulating drug‐related product. There were 7 treatment‐emergent adverse events, all of which were considered mild and not considered to be related to the study drug. Ziritaxestat is a novel inhibitor of autotaxin, an enzyme responsible for the production of lysophosphatidic acid, the downstream signaling of which mediates responses to tissue injury and has been implicated in the pathogenesis of fibrotic conditions such as idiopathic pulmonary fibrosis and systemic sclerosis. This study (Clinical Trial Registration: NCT03787186) was designed to assess the absorption, distribution, metabolism, and excretion of orally administered 600-mg ziritaxestat labeled with a carbon-14 tracer ( C-ziritaxestat). To understand the absolute bioavailability of ziritaxestat, an intravenous 100-μg microdose, labeled with a microtracer amount of C radiation, was administered in a separate part of the study, following an unlabeled 600-mg therapeutic oral dose of ziritaxestat. Six healthy male subjects completed each study part. The majority of the labeled oral dose was recovered in feces (77%), with a total mass balance of 84%. The absolute bioavailability of ziritaxestat was 54%. Ziritaxestat was the main (76%) circulating drug-related product. There were 7 treatment-emergent adverse events, all of which were considered mild and not considered to be related to the study drug. Ziritaxestat is a novel inhibitor of autotaxin, an enzyme responsible for the production of lysophosphatidic acid, the downstream signaling of which mediates responses to tissue injury and has been implicated in the pathogenesis of fibrotic conditions such as idiopathic pulmonary fibrosis and systemic sclerosis. This study (Clinical Trial Registration: NCT03787186) was designed to assess the absorption, distribution, metabolism, and excretion of orally administered 600-mg ziritaxestat labeled with a carbon-14 tracer (14 C-ziritaxestat). To understand the absolute bioavailability of ziritaxestat, an intravenous 100-μg microdose, labeled with a microtracer amount of 14 C radiation, was administered in a separate part of the study, following an unlabeled 600-mg therapeutic oral dose of ziritaxestat. Six healthy male subjects completed each study part. The majority of the labeled oral dose was recovered in feces (77%), with a total mass balance of 84%. The absolute bioavailability of ziritaxestat was 54%. Ziritaxestat was the main (76%) circulating drug-related product. There were 7 treatment-emergent adverse events, all of which were considered mild and not considered to be related to the study drug.Ziritaxestat is a novel inhibitor of autotaxin, an enzyme responsible for the production of lysophosphatidic acid, the downstream signaling of which mediates responses to tissue injury and has been implicated in the pathogenesis of fibrotic conditions such as idiopathic pulmonary fibrosis and systemic sclerosis. This study (Clinical Trial Registration: NCT03787186) was designed to assess the absorption, distribution, metabolism, and excretion of orally administered 600-mg ziritaxestat labeled with a carbon-14 tracer (14 C-ziritaxestat). To understand the absolute bioavailability of ziritaxestat, an intravenous 100-μg microdose, labeled with a microtracer amount of 14 C radiation, was administered in a separate part of the study, following an unlabeled 600-mg therapeutic oral dose of ziritaxestat. Six healthy male subjects completed each study part. The majority of the labeled oral dose was recovered in feces (77%), with a total mass balance of 84%. The absolute bioavailability of ziritaxestat was 54%. Ziritaxestat was the main (76%) circulating drug-related product. There were 7 treatment-emergent adverse events, all of which were considered mild and not considered to be related to the study drug. |
| Author | Helmer, Eric Shaw, Iain Delage, Stephane Willson, Ashley Westerhof, Mark Brearley, Christopher Sidhu, Sharan Cooke, Ray |
| AuthorAffiliation | 2 Quotient Sciences Nottingham UK 3 Galapagos NV Mechelen Belgium 4 Pharmaron Rushden UK 1 Galapagos Biotech Limited Cambridge UK |
| AuthorAffiliation_xml | – name: 4 Pharmaron Rushden UK – name: 1 Galapagos Biotech Limited Cambridge UK – name: 2 Quotient Sciences Nottingham UK – name: 3 Galapagos NV Mechelen Belgium |
| Author_xml | – sequence: 1 givenname: Eric surname: Helmer fullname: Helmer, Eric email: ericghelmer@gmail.com organization: Galapagos Biotech Limited – sequence: 2 givenname: Ashley surname: Willson fullname: Willson, Ashley organization: Quotient Sciences – sequence: 3 givenname: Christopher surname: Brearley fullname: Brearley, Christopher organization: Galapagos NV – sequence: 4 givenname: Mark surname: Westerhof fullname: Westerhof, Mark organization: Galapagos NV – sequence: 5 givenname: Stephane surname: Delage fullname: Delage, Stephane organization: Galapagos NV – sequence: 6 givenname: Iain surname: Shaw fullname: Shaw, Iain organization: Quotient Sciences – sequence: 7 givenname: Ray surname: Cooke fullname: Cooke, Ray organization: Pharmaron – sequence: 8 givenname: Sharan surname: Sidhu fullname: Sidhu, Sharan organization: Quotient Sciences |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/34633152$$D View this record in MEDLINE/PubMed |
| BookMark | eNp9kU1PGzEQhq0KVCjl0D9QWeoFDgF_7delEgolIAWRA6qqXiyvd5aYeu1g70Jz7h-vt6FRi9T64pHmmVfvzPsG7TjvAKF3lJxQQtipXjVNqhh9hfYZzcmkyEW5s635lz10GOM9SS8nlFLxGu1xkXNOM7aPfiyWKnRK-2_GQW90xMo1-Bp6VXtrYod9i7-aYHr1HWKvenw0my9mNK_IMTYOX4Ky_XKNr5UF_NnbwfUAIeILb61_Mu4OX7k-qEdwfthI3wRl8VnTGWdi6vTGu7dot1U2wuHzf4BuLz7dTi8n85vZ1fRsPtFCcDrRRUl1IfJK17WAoqwz0ZStKpoS2rwkAKRoBQPdUk0byIu64oVqyybdQZfA-QH6uJFdDXUHjYbRmZWrYDoV1tIrI__uOLOUd_5RVqxijGdJ4OhZIPiHIZ1DdiZqsFY5SOtJlpWk4qzgRUI_vEDv_RBc2k6ynAlKeEZZot7_6Whr5Xc8CTjeADr4GAO0W4QSOaYvx_TlmH5iT1-wOqU23jctY-z_Jp6MhfW_peV0cX7-a-Iny8bCiQ |
| CitedBy_id | crossref_primary_10_1002_cpt_3138 crossref_primary_10_1016_j_chembiol_2022_12_006 crossref_primary_10_1002_cpt_2689 crossref_primary_10_3390_ijms25063212 crossref_primary_10_3390_ijms24129812 crossref_primary_10_3390_cancers15082299 crossref_primary_10_1111_cts_13622 |
| Cites_doi | 10.1111/cts.12549 10.1165/rcmb.2012-0235ED 10.1007/s40262-019-00755-3 10.1016/S0140-6736(17)30933-9 10.1007/s11095-018-2458-6 10.1093/rheumatology/kew224 10.1038/nm1685 10.1038/nrdp.2015.2 10.1124/dmd.119.088344 10.4321/S1130-01082012000400002 10.1002/art.39797 10.1136/bmjresp-2019-000422 10.1016/S0140-6736(11)60052-4 10.1002/art.41055 10.4155/bio.12.242 10.3390/jcm7080201 10.4155/tde.11.19 10.1211/jpp.61.05.0002 10.1023/A:1018943613122 10.1136/annrheumdis-2016-209909 10.1172/JCI31139 10.1111/j.1476-5381.2010.00828.x 10.3389/fmed.2018.00180 10.1186/s12931-020-1275-8 10.1165/rcmb.2012-0004OC 10.1164/rccm.201506-1063ST 10.1002/jcph.1424 10.1016/S2213-2600(18)30181-4 10.1002/art.30262 10.2165/00003088-200241100-00005 10.1080/00498254.2016.1179821 10.1056/NEJMra003200 10.1136/gut.27.8.886 |
| ContentType | Journal Article |
| Copyright | 2021 Galapagos NV. published by Wiley Periodicals LLC on behalf of American College of Clinical Pharmacology 2021 Galapagos NV. Clinical Pharmacology in Drug Development published by Wiley Periodicals LLC on behalf of American College of Clinical Pharmacology. 2021. This article is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License. |
| Copyright_xml | – notice: 2021 Galapagos NV. published by Wiley Periodicals LLC on behalf of American College of Clinical Pharmacology – notice: 2021 Galapagos NV. Clinical Pharmacology in Drug Development published by Wiley Periodicals LLC on behalf of American College of Clinical Pharmacology. – notice: 2021. This article is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License. |
| DBID | 24P AAYXX CITATION CGR CUY CVF ECM EIF NPM K9. 7X8 5PM |
| DOI | 10.1002/cpdd.1021 |
| DatabaseName | Wiley Online Library Open Access CrossRef Medline MEDLINE MEDLINE (Ovid) MEDLINE MEDLINE PubMed ProQuest Health & Medical Complete (Alumni) MEDLINE - Academic PubMed Central (Full Participant titles) |
| DatabaseTitle | CrossRef MEDLINE Medline Complete MEDLINE with Full Text PubMed MEDLINE (Ovid) ProQuest Health & Medical Complete (Alumni) MEDLINE - Academic |
| DatabaseTitleList | CrossRef ProQuest Health & Medical Complete (Alumni) MEDLINE MEDLINE - Academic |
| Database_xml | – sequence: 1 dbid: 24P name: Wiley Online Library Open Access url: https://authorservices.wiley.com/open-science/open-access/browse-journals.html sourceTypes: Publisher – sequence: 2 dbid: NPM name: PubMed url: https://proxy.k.utb.cz/login?url=http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed sourceTypes: Index Database – sequence: 3 dbid: EIF name: MEDLINE url: https://proxy.k.utb.cz/login?url=https://www.webofscience.com/wos/medline/basic-search sourceTypes: Index Database |
| DeliveryMethod | fulltext_linktorsrc |
| Discipline | Pharmacy, Therapeutics, & Pharmacology |
| DocumentTitleAlternate | Helmer et al |
| EISSN | 2160-7648 |
| EndPage | 256 |
| ExternalDocumentID | PMC9292235 34633152 10_1002_cpdd_1021 CPDD1021 |
| Genre | article Clinical Study Research Support, Non-U.S. Gov't Journal Article |
| GroupedDBID | -MK 05W 0R~ 1OC 24P 33P 3SF 52U 52V 53G 8-1 AAESR AAEVG AAHHS AAHQN AAIPD AAMNL AANHP AANLZ AAONW AAXRX AAYCA AAZKR ABCUV ABDBF ABJNI ABQWH ABXGK ACAHQ ACBWZ ACCFJ ACCZN ACGFS ACGOF ACMXC ACPOU ACRPL ACUHS ACXBN ACXQS ACYXJ ADBBV ADBTR ADEOM ADIZJ ADKYN ADMGS ADNMO ADOZA ADXAS ADZMN ADZOD AEEZP AEIGN AEIMD AENEX AEQDE AEUYR AFBPY AFFPM AFGKR AFPWT AFWVQ AHBTC AIACR AITYG AIURR AIWBW AJBDE ALMA_UNASSIGNED_HOLDINGS ALUQN ALVPJ AMBMR AMYDB ASPBG ATUGU AVWKF AZFZN AZVAB BDRZF BFHJK BHBCM BMXJE BNHUX BOGZA BRXPI C45 DCZOG DPXWK DRFUL DRMAN DRSTM EBS EJD FUBAC G-S GODZA H13 HGLYW KBYEO LATKE LEEKS LH4 LITHE LOXES LSO LUTES LW6 LYRES MEWTI MRFUL MRMAN MRSTM MSFUL MSMAN MSSTM MXFUL MXMAN MXSTM MY~ O66 O9- OVD P2W PQQKQ R.K ROL SUPJJ TEORI TUS WBKPD WIH WIJ WIK WOHZO WOIKV WPGGZ WXSBR WYJ ZZTAW AAYXX AEYWJ AGHNM AGQPQ AGYGG CITATION AAMMB AEFGJ AGXDD AIDQK AIDYY CGR CUY CVF ECM EIF NPM K9. 7X8 5PM |
| ID | FETCH-LOGICAL-c4431-c781c7469cbb4e78b54d8fa7d8ef680ee07f42ecf1c1de67b937af8d160c8e33 |
| IEDL.DBID | 24P |
| ISSN | 2160-763X 2160-7648 |
| IngestDate | Thu Aug 21 18:07:16 EDT 2025 Fri Jul 11 08:12:09 EDT 2025 Mon Jul 14 07:50:26 EDT 2025 Mon Jul 21 06:00:35 EDT 2025 Tue Jul 01 00:19:14 EDT 2025 Thu Apr 24 23:01:18 EDT 2025 Wed Jan 22 16:27:33 EST 2025 |
| IsDoiOpenAccess | true |
| IsOpenAccess | true |
| IsPeerReviewed | true |
| IsScholarly | true |
| Issue | 2 |
| Keywords | mass balance ADME IPF systemic scleroses ziritaxestat |
| Language | English |
| License | Attribution 2021 Galapagos NV. Clinical Pharmacology in Drug Development published by Wiley Periodicals LLC on behalf of American College of Clinical Pharmacology. This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
| LinkModel | DirectLink |
| MergedId | FETCHMERGED-LOGICAL-c4431-c781c7469cbb4e78b54d8fa7d8ef680ee07f42ecf1c1de67b937af8d160c8e33 |
| Notes | Affiliation was Galapagos Biotech Limited at the time of study conduct and manuscript development. Current address for Eric Helmer: Exscientia, 15 Overton Drive, Thame OX9 3YJ, UK ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23 |
| OpenAccessLink | https://onlinelibrary.wiley.com/doi/abs/10.1002%2Fcpdd.1021 |
| PMID | 34633152 |
| PQID | 2624103512 |
| PQPubID | 2034576 |
| PageCount | 11 |
| ParticipantIDs | pubmedcentral_primary_oai_pubmedcentral_nih_gov_9292235 proquest_miscellaneous_2580932737 proquest_journals_2624103512 pubmed_primary_34633152 crossref_primary_10_1002_cpdd_1021 crossref_citationtrail_10_1002_cpdd_1021 wiley_primary_10_1002_cpdd_1021_CPDD1021 |
| ProviderPackageCode | CITATION AAYXX |
| PublicationCentury | 2000 |
| PublicationDate | February 2022 |
| PublicationDateYYYYMMDD | 2022-02-01 |
| PublicationDate_xml | – month: 02 year: 2022 text: February 2022 |
| PublicationDecade | 2020 |
| PublicationPlace | United States |
| PublicationPlace_xml | – name: United States – name: Oxford – name: Hoboken |
| PublicationTitle | Clinical pharmacology in drug development |
| PublicationTitleAlternate | Clin Pharmacol Drug Dev |
| PublicationYear | 2022 |
| Publisher | Wiley Subscription Services, Inc John Wiley and Sons Inc |
| Publisher_xml | – name: Wiley Subscription Services, Inc – name: John Wiley and Sons Inc |
| References | 2015; 1 2011; 378 2019; 6 2011; 2 2017; 47 2009; 61 2019; 59 2019; 58 2008; 14 2017; 390 2020; 72(suppl. 10) 2010; 160 2012; 104 2001; 345 2016; 55 2018; 7 2018; 6 2015; 192 2018; 5 2007; 117 2002; 41 1993; 10 2017; 76 2019; 47 1986; 27 2011; 63 2020; 21 2012; 47 2018; 11 2012; 4 2016; 68 2018; 35 e_1_2_10_23_1 e_1_2_10_24_1 e_1_2_10_22_1 e_1_2_10_20_1 e_1_2_10_2_1 e_1_2_10_4_1 e_1_2_10_18_1 e_1_2_10_3_1 e_1_2_10_19_1 e_1_2_10_6_1 e_1_2_10_16_1 e_1_2_10_5_1 e_1_2_10_17_1 Khanna D (e_1_2_10_21_1) 2020; 72 e_1_2_10_8_1 e_1_2_10_14_1 e_1_2_10_7_1 e_1_2_10_15_1 e_1_2_10_12_1 e_1_2_10_9_1 e_1_2_10_13_1 e_1_2_10_34_1 e_1_2_10_10_1 e_1_2_10_33_1 e_1_2_10_11_1 e_1_2_10_32_1 e_1_2_10_31_1 e_1_2_10_30_1 e_1_2_10_29_1 e_1_2_10_27_1 e_1_2_10_28_1 e_1_2_10_25_1 e_1_2_10_26_1 |
| References_xml | – volume: 21 start-page: 25 issue: 1 year: 2020 article-title: Azithromycin has enhanced effects on lung fibroblasts from idiopathic pulmonary fibrosis (IPF) patients compared to controls publication-title: Respir Res – volume: 5 start-page: 180 year: 2018 article-title: Autotaxin in pathophysiology and pulmonary fibrosis publication-title: Front Med (Lausanne) – volume: 47 start-page: 217 issue: 3 year: 2017 end-page: 229 article-title: Absorption, distribution, metabolism and excretion (ADME) of the ALK inhibitor alectinib: results from an absolute bioavailability and mass balance study in healthy subjects publication-title: Xenobiotica – volume: 117 start-page: 557 issue: 3 year: 2007 end-page: 567 article-title: Systemic sclerosis: a prototypic multisystem fibrotic disorder publication-title: J Clin Invest – volume: 104 start-page: 165 issue: 4 year: 2012 end-page: 184 article-title: Drug dosage recommendations in patients with chronic liver disease publication-title: Rev Esp Enferm Dig – volume: 35 start-page: 182 issue: 9 year: 2018 article-title: Characterization of intestinal and hepatic CYP3A‐mediated metabolism of midazolam in children using a physiological population pharmacokinetic modelling approach publication-title: Pharm Res – volume: 72(suppl. 10) start-page: L09 year: 2020 article-title: A phase 2a randomized, double‐blind, placebo‐controlled study of ziritaxestat in early diffuse cutaneous systemic sclerosis (NOVESA) publication-title: Arthritis Rheumatol – volume: 6 issue: 1 year: 2019 article-title: Rationale, design and objectives of two phase III, randomised, placebo‐controlled studies of GLPG1690, a novel autotaxin inhibitor, in idiopathic pulmonary fibrosis (ISABELA 1 and 2) publication-title: BMJ Open Respir Res – volume: 41 start-page: 751 issue: 10 year: 2002 end-page: 790 article-title: Enterohepatic circulation: physiological, pharmacokinetic and clinical implications publication-title: Clin Pharmacokinet – volume: 160 start-page: 1699 issue: 7 year: 2010 end-page: 1713 article-title: A novel, orally active LPA(1) receptor antagonist inhibits lung fibrosis in the mouse bleomycin model publication-title: Br J Pharmacol – volume: 14 start-page: 45 issue: 1 year: 2008 end-page: 54 article-title: The lysophosphatidic acid receptor LPA1 links pulmonary fibrosis to lung injury by mediating fibroblast recruitment and vascular leak publication-title: Nat Med – volume: 58 start-page: 1175 issue: 9 year: 2019 end-page: 1191 article-title: Population pharmacokinetic and pharmacodynamic analysis of GLPG1690, an autotaxin inhibitor, in healthy volunteers and patients with idiopathic pulmonary fibrosis publication-title: Clin Pharmacokinet – volume: 47 start-page: 1457 issue: 12 year: 2019 end-page: 1468 article-title: An innovative approach to characterize clinical ADME and pharmacokinetics of the inhaled drug nemiralisib using an intravenous microtracer combined with an inhaled dose and an oral radiolabel dose in healthy male subjects publication-title: Drug Metab Dispos – volume: 7 issue: 8 year: 2018 article-title: Idiopathic pulmonary fibrosis (IPF): an overview publication-title: J Clin Med – volume: 47 start-page: 566 issue: 5 year: 2012 end-page: 574 article-title: Pulmonary autotaxin expression contributes to the pathogenesis of pulmonary fibrosis publication-title: Am J Respir Cell Mol Biol – volume: 192 start-page: e3 issue: 2 year: 2015 end-page: e19 article-title: An official ATS/ERS/JRS/ALAT Clinical Practice Guideline: treatment of idiopathic pulmonary fibrosis. an update of the 2011 clinical practice guideline publication-title: Am J Respir Crit Care Med – volume: 1 year: 2015 article-title: Systemic sclerosis publication-title: Nat Rev Dis Primers – volume: 11 start-page: 405 issue: 4 year: 2018 end-page: 411 article-title: Novel application of the two‐period microtracer approach to determine absolute oral bioavailability and fraction absorbed of ertugliflozin publication-title: Clin Transl Sci – volume: 378 start-page: 1949 issue: 9807 year: 2011 end-page: 1961 article-title: Idiopathic pulmonary fibrosis publication-title: Lancet – volume: 6 start-page: 627 issue: 8 year: 2018 end-page: 635 article-title: Safety, tolerability, pharmacokinetics, and pharmacodynamics of GLPG1690, a novel autotaxin inhibitor, to treat idiopathic pulmonary fibrosis (FLORA): a phase 2a randomised placebo‐controlled trial publication-title: Lancet Respir Med – volume: 390 start-page: 1685 issue: 10103 year: 2017 end-page: 1699 article-title: Systemic sclerosis publication-title: Lancet – volume: 61 start-page: 541 issue: 5 year: 2009 end-page: 558 article-title: Cytochrome P450‐mediated metabolism in the human gut wall publication-title: J Pharm Pharmacol – volume: 59 start-page: 1366 issue: 10 year: 2019 end-page: 1378 article-title: Safety, pharmacokinetics, and pharmacodynamics of the autotaxin inhibitor GLPG1690 in healthy subjects: phase 1 randomized trials publication-title: J Clin Pharmacol – volume: 63 start-page: 1405 issue: 5 year: 2011 end-page: 1415 article-title: Amelioration of dermal fibrosis by genetic deletion or pharmacologic antagonism of lysophosphatidic acid receptor 1 in a mouse model of scleroderma publication-title: Arthritis Rheum – volume: 10 start-page: 1093 issue: 7 year: 1993 end-page: 1095 article-title: Physiological parameters in laboratory animals and humans publication-title: Pharm Res – volume: 345 start-page: 517 issue: 7 year: 2001 end-page: 525 article-title: Idiopathic pulmonary fibrosis publication-title: N Engl J Med – volume: 76 start-page: 1327 issue: 8 year: 2017 end-page: 1339 article-title: Update of EULAR recommendations for the treatment of systemic sclerosis publication-title: Ann Rheum Dis – volume: 2 start-page: 643 issue: 5 year: 2011 end-page: 672 article-title: Flip‐flop pharmacokinetics–delivering a reversal of disposition: challenges and opportunities during drug development publication-title: Ther Deliv – volume: 55 start-page: 1906 issue: 10 year: 2016 end-page: 1910 article-title: BSR and BHPR guideline for the treatment of systemic sclerosis publication-title: Rheumatology (Oxford) – volume: 47 start-page: 563 issue: 5 year: 2012 end-page: 565 article-title: Autotaxin emerges as a therapeutic target for idiopathic pulmonary fibrosis: limiting fibrosis by limiting lysophosphatidic acid synthesis publication-title: Am J Respir Cell Mol Biol – volume: 27 start-page: 886 issue: 8 year: 1986 end-page: 892 article-title: Transit of pharmaceutical dosage forms through the small intestine publication-title: Gut – volume: 68 start-page: 2964 issue: 12 year: 2016 end-page: 2974 article-title: An autotaxin/lysophosphatidic acid/interleukin‐6 amplification loop drives scleroderma fibrosis publication-title: Arthritis Rheumatol – volume: 4 start-page: 2669 issue: 22 year: 2012 end-page: 2679 article-title: European Bioanalysis Forum recommendation: scientific validation of quantification by accelerator mass spectrometry publication-title: Bioanalysis – ident: e_1_2_10_34_1 doi: 10.1111/cts.12549 – ident: e_1_2_10_12_1 doi: 10.1165/rcmb.2012-0235ED – ident: e_1_2_10_18_1 doi: 10.1007/s40262-019-00755-3 – ident: e_1_2_10_7_1 doi: 10.1016/S0140-6736(17)30933-9 – ident: e_1_2_10_25_1 doi: 10.1007/s11095-018-2458-6 – ident: e_1_2_10_10_1 doi: 10.1093/rheumatology/kew224 – ident: e_1_2_10_13_1 doi: 10.1038/nm1685 – ident: e_1_2_10_8_1 doi: 10.1038/nrdp.2015.2 – ident: e_1_2_10_23_1 doi: 10.1124/dmd.119.088344 – ident: e_1_2_10_29_1 doi: 10.4321/S1130-01082012000400002 – ident: e_1_2_10_16_1 doi: 10.1002/art.39797 – ident: e_1_2_10_28_1 doi: 10.1136/bmjresp-2019-000422 – ident: e_1_2_10_3_1 doi: 10.1016/S0140-6736(11)60052-4 – volume: 72 start-page: L09 year: 2020 ident: e_1_2_10_21_1 article-title: A phase 2a randomized, double‐blind, placebo‐controlled study of ziritaxestat in early diffuse cutaneous systemic sclerosis (NOVESA) publication-title: Arthritis Rheumatol doi: 10.1002/art.41055 – ident: e_1_2_10_24_1 doi: 10.4155/bio.12.242 – ident: e_1_2_10_4_1 doi: 10.3390/jcm7080201 – ident: e_1_2_10_33_1 doi: 10.4155/tde.11.19 – ident: e_1_2_10_32_1 doi: 10.1211/jpp.61.05.0002 – ident: e_1_2_10_26_1 doi: 10.1023/A:1018943613122 – ident: e_1_2_10_27_1 doi: 10.1136/annrheumdis-2016-209909 – ident: e_1_2_10_9_1 doi: 10.1172/JCI31139 – ident: e_1_2_10_14_1 doi: 10.1111/j.1476-5381.2010.00828.x – ident: e_1_2_10_11_1 doi: 10.3389/fmed.2018.00180 – ident: e_1_2_10_5_1 doi: 10.1186/s12931-020-1275-8 – ident: e_1_2_10_17_1 doi: 10.1165/rcmb.2012-0004OC – ident: e_1_2_10_6_1 doi: 10.1164/rccm.201506-1063ST – ident: e_1_2_10_19_1 doi: 10.1002/jcph.1424 – ident: e_1_2_10_20_1 doi: 10.1016/S2213-2600(18)30181-4 – ident: e_1_2_10_15_1 doi: 10.1002/art.30262 – ident: e_1_2_10_30_1 doi: 10.2165/00003088-200241100-00005 – ident: e_1_2_10_22_1 doi: 10.1080/00498254.2016.1179821 – ident: e_1_2_10_2_1 doi: 10.1056/NEJMra003200 – ident: e_1_2_10_31_1 doi: 10.1136/gut.27.8.886 |
| SSID | ssj0000601114 |
| Score | 2.2509937 |
| Snippet | Ziritaxestat is a novel inhibitor of autotaxin, an enzyme responsible for the production of lysophosphatidic acid, the downstream signaling of which mediates... |
| SourceID | pubmedcentral proquest pubmed crossref wiley |
| SourceType | Open Access Repository Aggregation Database Index Database Enrichment Source Publisher |
| StartPage | 246 |
| SubjectTerms | ADME Administration, Oral Bioavailability Carbon Radioisotopes Drug dosages Healthy Volunteers Humans Imidazoles IPF Male mass balance Metabolism Original Pharmacokinetics Pyrimidines systemic scleroses ziritaxestat |
| Title | Pharmacokinetics and Metabolism of Ziritaxestat (GLPG1690) in Healthy Male Volunteers Following Intravenous and Oral Administration |
| URI | https://onlinelibrary.wiley.com/doi/abs/10.1002%2Fcpdd.1021 https://www.ncbi.nlm.nih.gov/pubmed/34633152 https://www.proquest.com/docview/2624103512 https://www.proquest.com/docview/2580932737 https://pubmed.ncbi.nlm.nih.gov/PMC9292235 |
| Volume | 11 |
| hasFullText | 1 |
| inHoldings | 1 |
| isFullTextHit | |
| isPrint | |
| link | http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwjZ3Lb9NAEIdHVXvhgnhjKNWCUFWkWrV3be9anNqGtCACPgQUcbG8D4uI4lRNeOTMP87MOnaIChK3RJ4ka89M5re7ns8AzwnipWSehzqTEU5QMhNiHVehrXUe5VrExgNMR--y8w_Jm0k62YKXXS9My4foF9woM_z_NSV4pedHa2ioubSWwAM49dmh1loC5_Ok6BdYCDQSe7Y3j7MoxDyadGShiB_1n96sR9dE5vV7Jf_UsL4IDW_BzZV6ZMetu2_DlmvuwH7R4qeXh2y87qaaH7J9VqzB1Mu78Kt7-wVPnkxY1Vg2cgsMhIvp_Cub1ezTlFYLfjpqNGIHZ2-LM9rhesGmDWs7lpZshDWFfcSQRZ-geGRDDKXZDyyB7DUN_runvvqvfn9Fg93A896D8fDV-PQ8XD2EITQJiovQSBUbiZNoo3XipNJpYlVdSatcnanIuUjWCXemjk1sXSY16p2qVhavuVFOiPuw3cwa9xCYEKk2pBGqSiepyVVeR2klLFeVJW8FcNB5ojQrQDk9J-OibNHKvCSnleS0AJ71ppctleNvRrudO8tVYs5LnqFkod1THsDT_jCmFO2TVI3DC1TyVEUoa6WQATxovd__ikgyIVDzBCA34qI3IFz35pFm-tlju1GIohZL8TR9BP174OVpMRjQi0f_b_oYbnBqzPD3k-_C9uLqm3uCcmmh93xa7MHO8cngZPgbSigUNA |
| linkProvider | Wiley-Blackwell |
| linkToHtml | http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwjZ3Lb9NAEIdXVTnABfHGUGBBqCpSrdq7a-9a6qVqSVNIig8BRVws78NqRHGqJjxy7j_emXXsEBUkbok8Sdaemcxvdz2fCXmLEC8lsyzUqYxggpKaEOq4Cm2lsyjTPDYeYDo8TfufxYdxMt4g-20vTMOH6BbcMDP8_zUmOC5I762ooebCWiQPwNznlkiZxLRkIu9WWJA0Enu4N4vTKIREGrdooYjtdZ9eL0g3VObNmyX_FLG-CvXukbtL-UgPGn_fJxuufkC284Y_vdilo1U71WyXbtN8RaZePCRX7dtvcPZoQsva0qGbQyScT2bf6bSiXye4XPDbYacR3Tke5Me4xfWOTmratCwt6BCKCv0CMQtOAfVIexBL019QA-kJDv6nx776r_50iYNd4_M-IqPe-9FhP1w-hSE0AtRFaKSKjYRZtNFaOKl0IqyqSmmVq1IVORfJSjBnqtjE1qVSg-ApK2XhmhvlOH9MNutp7Z4SynmiDYqEstQiMZnKqigpuWWqtOitgOy0nijMklCOD8o4Lxq2MivQaQU6LSBvOtOLBsvxN6Ot1p3FMjNnBUtBs-D2KQvI6-4w5BRulJS1gwtUsERFoGsllwF50ni_-xUuUs5B9ARErsVFZ4C87vUj9eTMc7tBiYIYS-A0fQT9e-DFYX50hC-e_b_pK3K7PxoOisHJ6cfn5A7DLg1_c_kW2Zxf_nAvQDvN9UufItd3gxYu |
| linkToPdf | http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwjZ3fb9MwEMetaUiIF8RvAgMMQtOQFi2xk9jRnqaVboN15KGgihcr_hGtYqTVWn70ef_47pwmpRpIvLXKtXVyd72v7dwnhLxFiJcUeR7qTEQwQclMCHVchrbSeZRrHhsPMB2cZcefkw-jdLRB9ttemIYP0S24YWb4_2tM8Kmt9lbQUDO1FsEDMPW55Tf7EOucFN0CC4JGYs_2ZnEWhZBHo5YsFLG97tPr9eiGyLx5r-SfGtYXof49cnepHulB4-77ZMPVD8h20eCnF7t0uOqmmu3SbVqswNSLh-SqffsNTh5NaFlbOnBzCISL8ew7nVT06xhXC347bDSiO0enxRHucL2j45o2HUsLOoCaQr9AyIJPQDzSPoTS5BeUQHqCg__pqa_-qz9d4mDX8LyPyLD_fnh4HC4fwhCaBMRFaISMjYBJtNE6cULqNLGyKoWVrspk5FwkqoQ5U8Umti4TGvROWUkL19xIx_ljsllPaveUUM5TbVAjlKVOUpPLvIrSklsmS4veCshO6wllloByfE7GhWrQykyh0xQ6LSBvOtNpQ-X4m9FW6061TMyZYhlIFtw9ZQF53R2GlMJ9krJ2cIEUS2UEslZwEZAnjfe7X-FJxjlonoCItbjoDBDXvX6kHp97bDcIUdBiKZymj6B_D1wdFr0evnj2_6avyO2i11enJ2cfn5M7DHs0_K3lW2RzfvnDvQDlNNcvfYZcA8sXFWA |
| openUrl | ctx_ver=Z39.88-2004&ctx_enc=info%3Aofi%2Fenc%3AUTF-8&rfr_id=info%3Asid%2Fsummon.serialssolutions.com&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Pharmacokinetics+and+Metabolism+of+Ziritaxestat+%28GLPG1690%29+in+Healthy+Male+Volunteers+Following+Intravenous+and+Oral+Administration&rft.jtitle=Clinical+pharmacology+in+drug+development&rft.au=Helmer%2C+Eric&rft.au=Willson%2C+Ashley&rft.au=Brearley%2C+Christopher&rft.au=Westerhof%2C+Mark&rft.date=2022-02-01&rft.issn=2160-7648&rft.eissn=2160-7648&rft.volume=11&rft.issue=2&rft.spage=246&rft_id=info:doi/10.1002%2Fcpdd.1021&rft.externalDBID=NO_FULL_TEXT |
| thumbnail_l | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/lc.gif&issn=2160-763X&client=summon |
| thumbnail_m | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/mc.gif&issn=2160-763X&client=summon |
| thumbnail_s | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/sc.gif&issn=2160-763X&client=summon |