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Fifteen healthy subjects, 13 patients with controlled SLE (SLEDAI 0\u20134), and 12 patients with uncontrolled SLE (SLEDAI from 6 to 15), all women, were investigated. Apparent total clearance of midazolam (MDZ), a marker of CYP3A4 activity, did not vary among the three investigated groups. The controlled and uncontrolled SLE groups showed higher plasma concentrations of MCP\u20101 and TNF\u2010\u03b1, while the uncontrolled SLE group also showed higher plasma concentrations of IL\u201010. The uncontrolled SLE group showed higher area under the curve (AUC) for ATV (60.47 (43.76\u201383.56) vs. 30.56 (22.69\u201341.15) ng\u22c5hour\/mL) and its inactive metabolite ATV\u2010lactone (98.74 (74.31\u2013131.20) vs. 49.21 (34.89\u201369.42) ng\u22c5hour\/mL), and lower apparent total clearance (330.7 (239.30\u2013457.00) vs. 654.5 (486.00\u2013881.4) L\/hour) and apparent volume of distribution (2,609 (1,607\u20134,234) vs. 7,159 (4,904\u201310,450) L), when compared to the healthy subjects group (geometric mean and 95% confidence interval). The pharmacokinetics of ATV and its metabolites did not differ between the healthy subject group and the patients with controlled SLE group. In conclusion, uncontrolled SLE increased the systemic exposure to both ATV and ATV\u2010lactone, inferring inhibition of OATP1B1 activity, once <jats:italic>in vivo<\/jats:italic> CYP3A4 activity assessed by oral clearance of MDZ was unaltered. The inflammatory state, not the disease itself, was responsible for the changes described in the uncontrolled SLE group as a consequence of inhibition of OATP1B1, because systemic exposure to ATV and its metabolites were not altered in patients with controlled SLE.<\/jats:p>","DOI":"10.1111\/cts.12808","type":"journal-article","created":{"date-parts":[[2020,5,28]],"date-time":"2020-05-28T13:31:57Z","timestamp":1590672717000},"page":"1227-1235","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Systemic Lupus Erythematosus Activity Affects the Sinusoidal Uptake Transporter OATP1B1 Evaluated by the Pharmacokinetics of Atorvastatin"],"prefix":"10.1111","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1004-8916","authenticated-orcid":false,"given":"Roberta Nat\u00e1lia","family":"Cestari","sequence":"first","affiliation":[{"name":"Department of Clinical Analyses, Toxicology and Food Science School of Pharmaceutical Sciences of Ribeirao Preto University of Sao Paulo Ribeirao Preto Sao Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ren\u00ea Donizeti Ribeiro","family":"de Oliveira","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine Ribeirao Preto Medical School University of Sao Paulo Ribeirao Preto Sao Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fl\u00e1vio Falc\u00e3o Lima","family":"de Souza","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine Ribeirao Preto Medical School University of Sao Paulo Ribeirao Preto Sao Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2782-0389","authenticated-orcid":false,"given":"Leandro Francisco","family":"Pippa","sequence":"additional","affiliation":[{"name":"Department of Clinical Analyses, Toxicology and Food Science School of Pharmaceutical Sciences of Ribeirao Preto University of Sao Paulo Ribeirao Preto Sao Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7024-4252","authenticated-orcid":false,"given":"Glauco Henrique Balthazar","family":"Nardotto","sequence":"additional","affiliation":[{"name":"Department of Clinical Analyses, Toxicology and Food Science School of Pharmaceutical Sciences of Ribeirao Preto University of Sao Paulo Ribeirao Preto Sao Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adriana","family":"Rocha","sequence":"additional","affiliation":[{"name":"Department of Clinical Analyses, Toxicology and Food Science School of Pharmaceutical Sciences of Ribeirao Preto University of Sao Paulo Ribeirao Preto Sao Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eduardo Ant\u00f4nio","family":"Donadi","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine Ribeirao Preto Medical School University of Sao Paulo Ribeirao Preto Sao Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0074-4953","authenticated-orcid":false,"given":"Vera Lucia","family":"Lanchote","sequence":"additional","affiliation":[{"name":"Department of Clinical Analyses, Toxicology and Food Science School of Pharmaceutical Sciences of Ribeirao Preto University of Sao Paulo Ribeirao Preto Sao Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,5,28]]},"reference":[{"key":"e_1_2_9_1_1","doi-asserted-by":"publisher","DOI":"10.1080\/17425255.2017.1311323"},{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1517\/17425255.2011.553600"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/clpt.2013.79"},{"key":"e_1_2_9_4_1","first-page":"539","article-title":"Increased concentration of proatherogenic inflammatory cytokines in systemic lupus erythematosus: relationship to cardiovascular risk factors","volume":"33","author":"Asanuma Y.","year":"2006","journal-title":"J. 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