{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T01:24:44Z","timestamp":1789521884304,"version":"build-2803163510"},"reference-count":58,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2021,11,23]],"date-time":"2021-11-23T00:00:00Z","timestamp":1637625600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003134","name":"Fonds pour la Formation \u00e0 la Recherche dans l\u2019Industrie et dans l\u2019Agriculture","doi-asserted-by":"publisher","award":["FC16749"],"award-info":[{"award-number":["FC16749"]}],"id":[{"id":"10.13039\/501100003134","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003134","name":"Fonds pour la Formation \u00e0 la Recherche dans l\u2019Industrie et dans l\u2019Agriculture","doi-asserted-by":"publisher","award":["FC33437"],"award-info":[{"award-number":["FC33437"]}],"id":[{"id":"10.13039\/501100003134","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Translational Sci"],"published-print":{"date-parts":[[2022,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The purpose of this study was to investigate the potential clinical relevance of estimating the apparent clearance (CL\/F) of atorvastatin through population pharmacokinetic (PopPK) modeling with samples collected in a real\u2010life setting in a cohort of ambulatory patients at risk of cardiovascular disease by using an opportunistic sampling strategy easily accessible in clinical routine. A total of 132 pharmacokinetic (PK) samples at a maximum of three visits were collected in the 70 included patients. The effects of demographic, genetic, and clinical covariates were also considered. With the collected data, we developed a two\u2010compartment PopPK model that allowed estimating atorvastatin CL\/F relatively precisely and considering the genotype of the patient for <jats:italic>SLCO1B1<\/jats:italic> c.521T&gt;C single\u2010nucleotide polymorphism (SNP). Our results indicate that the estimation of the CL\/F of atorvastatin through our PopPK model might help in identifying patients at risk of myalgia. Indeed, we showed that a patient presenting a CL\/F lower than 414.67\u00a0L\u00a0h<jats:sup>\u22121<\/jats:sup> is at risk of suffering from muscle discomfort. We also observed that the CL\/F was correlated with the efficacy outcomes, suggesting that a higher CL\/F is associated with a better drug efficacy (i.e., a greater decrease in total and LDL\u2010cholesterol levels). In conclusion, our study demonstrates that PopPK modeling can be useful in daily clinics to estimate a patient\u2019 atorvastatin clearance. Notifying the clinician with this information can help in identifying patients at risk of myalgia and gives indication about the potential responsiveness to atorvastatin therapy.<\/jats:p>","DOI":"10.1111\/cts.13185","type":"journal-article","created":{"date-parts":[[2021,11,11]],"date-time":"2021-11-11T07:04:38Z","timestamp":1636614278000},"page":"667-679","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Atorvastatin population pharmacokinetics in a real\u2010life setting: Influence of genetic polymorphisms and association with clinical response"],"prefix":"10.1111","volume":"15","author":[{"given":"Gabriel","family":"Stillemans","sequence":"first","affiliation":[{"name":"Integrated PharmacoMetrics, PharmacoGenomics and PharmacoKinetics Louvain Drug Research Institute Universit\u00e9 catholique de Louvain  Brussels Belgium"},{"name":"Louvain Centre for Toxicology and Applied Pharmacology Institut de Recherche Exp\u00e9rimentale et Clinique Universit\u00e9 Catholique de Louvain  Brussels Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adrien","family":"Paquot","sequence":"additional","affiliation":[{"name":"Bioanalysis and Pharmacology of Bioactive Lipids Louvain Drug Research Institute Universit\u00e9 Catholique de Louvain  Brussels Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giulio G.","family":"Muccioli","sequence":"additional","affiliation":[{"name":"Bioanalysis and Pharmacology of Bioactive Lipids Louvain Drug Research Institute Universit\u00e9 Catholique de Louvain  Brussels Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emilia","family":"Hoste","sequence":"additional","affiliation":[{"name":"Integrated PharmacoMetrics, PharmacoGenomics and PharmacoKinetics Louvain Drug Research Institute Universit\u00e9 catholique de Louvain  Brussels Belgium"},{"name":"Louvain Centre for Toxicology and Applied Pharmacology Institut de Recherche Exp\u00e9rimentale et Clinique Universit\u00e9 Catholique de Louvain  Brussels Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nadtha","family":"Panin","sequence":"additional","affiliation":[{"name":"Louvain Centre for Toxicology and Applied Pharmacology Institut de Recherche Exp\u00e9rimentale et Clinique Universit\u00e9 Catholique de Louvain  Brussels Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anders","family":"\u00c5sberg","sequence":"additional","affiliation":[{"name":"Department of Pharmacology School of Pharmacy University of Oslo  Oslo Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean\u2010Luc","family":"Balligand","sequence":"additional","affiliation":[{"name":"Pole of Pharmacology and Therapeutics Institut de Recherche Exp\u00e9rimentale et Clinique Universit\u00e9 Catholique de Louvain  Brussels Belgium"},{"name":"Department of Internal Medicine Cliniques Universitaires Saint\u2010Luc  Brussels Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincent","family":"Haufroid","sequence":"additional","affiliation":[{"name":"Louvain Centre for Toxicology and Applied Pharmacology Institut de Recherche Exp\u00e9rimentale et Clinique Universit\u00e9 Catholique de Louvain  Brussels Belgium"},{"name":"Department of Clinical Chemistry Cliniques Universitaires Saint\u2010Luc  Brussels Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laure","family":"Elens","sequence":"additional","affiliation":[{"name":"Integrated PharmacoMetrics, PharmacoGenomics and PharmacoKinetics Louvain Drug Research Institute Universit\u00e9 catholique de Louvain  Brussels Belgium"},{"name":"Louvain Centre for Toxicology and Applied Pharmacology Institut de Recherche Exp\u00e9rimentale et Clinique Universit\u00e9 Catholique de Louvain  Brussels Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,11,23]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehx144"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehw106"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/14651858.CD008226.pub3"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1517\/14740338.2011.540568"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.2165\/00003088-200342130-00005"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/j.1552-4604.2000.tb05987.x"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.amjcard.2005.12.013"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0009-9236(96)90218-0"},{"key":"e_1_2_8_10_1","first-page":"1369","article-title":"Lactonization is the critical first step in the disposition of the 3\u2010hydroxy\u20103\u2010methylglutaryl\u2010CoA reductase inhibitor atorvastatin","volume":"28","author":"Jacobsen W","year":"2000","journal-title":"Drug Metab Dispos"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejps.2007.12.009"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1023\/A:1018923325359"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1124\/dmd.104.002477"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.109.203596"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.taap.2013.03.019"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2006.03.003"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1124\/dmd.113.056309"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1080\/17425255.2020.1801634"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.2174\/1381612825666181219163534"},{"key":"e_1_2_8_20_1","first-page":"288","article-title":"Influence of SLCO1B1 polymorphisms on atorvastatin efficacy and safety in Macedonian subjects","volume":"72","author":"Mladenovska K","year":"2017","journal-title":"Pharmazie"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.2174\/1381612825666190705204614"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.2147\/DDDT.S131487"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1111\/jcpt.12369"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1139\/cjpp-2019-0339"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.2217\/pgs.15.47"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1159\/000445654"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40261-015-0317-3"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1111\/jcpt.12607"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12885-016-2062-2"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1097\/FPC.0000000000000252"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ihj.2018.07.009"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.18869\/acadpub.ibj.21.2.120"},{"key":"e_1_2_8_33_1","first-page":"1363","article-title":"Effects of two functionally important SLCO1B1 gene polymorphisms on pharmacokinetics of atorvastatin","volume":"30","author":"Rajput TA","year":"2017","journal-title":"Pak J Pharm Sci"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.2217\/pgs.14.138"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1038\/tpj.2011.59"},{"key":"e_1_2_8_36_1","first-page":"365","article-title":"The effect of SLCO1B1 polymorphism on the pharmacokinetics of atorvastatin and 2\u2010hydroxyatorvastatin in healthy Chinese people","volume":"72","author":"Wang Y","year":"2017","journal-title":"Pharmazie"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.clpt.6100220"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00228-014-1801-z"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.5414\/CPP48036"},{"key":"e_1_2_8_40_1","first-page":"480","article-title":"Effects of single nucleotide polymorphisms and haplotypes of the SLCO1B1 gene on the pharmacokinetic profile of atorvastatin in healthy Macedonian volunteers","volume":"70","author":"Daka A","year":"2015","journal-title":"Pharmazie"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13318-016-0383-9"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2019.109416"},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.1002\/psp4.12447"},{"key":"e_1_2_8_44_1","doi-asserted-by":"publisher","DOI":"10.3390\/pharmaceutics13050709"},{"key":"e_1_2_8_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejps.2015.06.019"},{"key":"e_1_2_8_46_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcph.66"},{"key":"e_1_2_8_47_1","doi-asserted-by":"publisher","DOI":"10.2165\/11535980-000000000-00000"},{"key":"e_1_2_8_48_1","doi-asserted-by":"publisher","DOI":"10.1038\/clpt.2009.100"},{"key":"e_1_2_8_49_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF03261933"},{"key":"e_1_2_8_50_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clpt.2006.02.014"},{"key":"e_1_2_8_51_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-6143.2005.01005.x"},{"key":"e_1_2_8_52_1","unstructured":"FDA.Drug development and drug interactions: table of substrates inhibitors and inducers.2021."},{"key":"e_1_2_8_53_1","unstructured":"pharmacoth\u00e9rapeutique C.b.d.i.R\u00e9pertoire Comment\u00e9 Des M\u00e9dicaments(2020)."},{"key":"e_1_2_8_54_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm300212s"},{"key":"e_1_2_8_55_1","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.113.208595"},{"key":"e_1_2_8_56_1","unstructured":"FDA.FDA label \u2010 Atorvastatin."},{"key":"e_1_2_8_57_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.fpc.0000170913.73780.5f"},{"key":"e_1_2_8_58_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.1820"},{"key":"e_1_2_8_59_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF03256413"}],"container-title":["Clinical and Translational Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cts.13185","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/cts.13185","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cts.13185","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,27]],"date-time":"2023-08-27T03:12:21Z","timestamp":1693105941000},"score":1,"resource":{"primary":{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/10.1111\/cts.13185"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,11,23]]},"references-count":58,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2022,3]]}},"alternative-id":["10.1111\/cts.13185"],"URL":"https:\/\/doi.org\/10.1111\/cts.13185","archive":["Portico"],"relation":{},"ISSN":["1752-8054","1752-8062"],"issn-type":[{"value":"1752-8054","type":"print"},{"value":"1752-8062","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,11,23]]},"assertion":[{"value":"2021-07-14","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-10-18","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-11-23","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}