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The aim of this study was to comprehensively investigate and characterise the clinical factors and comedications associated with circulating levels of ATV and its metabolites in secondary prevention clinical practice.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The plasma concentrations of ATV, 2\u2010hydroxy (2\u2010OH) ATV, ATV lactone (ATV L) and 2\u2010OH ATV L were determined in patients 1 month after hospitalisation for a non\u2010ST elevation acute coronary syndrome. Factors were identified using all subsets multivariable regression and model averaging with the Bayesian information criterion. Exploratory genotype\u2010stratified analyses were conducted using <jats:italic>ABCG2<\/jats:italic> rs2231142 (Q141K) and <jats:italic>CYP2C19<\/jats:italic> metaboliser status to further investigate novel associations.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>A total of 571 patients were included; 534 and 37 were taking ATV 80 mg and 40 mg daily, respectively. Clinical factors associated with ATV and\/or its metabolite levels included age, sex, body mass index and CYP3A inhibiting comedications. Smoking was newly associated with increased ATV lactonisation and reduced hydroxylation. Proton pump inhibitors (PPIs) and loop diuretics were newly associated with modestly increased levels of ATV (14% and 38%, respectively) and its metabolites. An interaction between PPIs and <jats:italic>CYP2C19<\/jats:italic> metaboliser status on exposure to specific ATV analytes (e.g. interaction <jats:italic>P<\/jats:italic> = .0071 for 2\u2010OH ATV L) was observed. Overall model R<jats:sup>2<\/jats:sup> values were 0.14\u20130.24.ConclusionMultiple factors were associated with circulating ATV and metabolite levels, including novel associations with smoking and drug\u2013drug(\u2013gene) interactions involving PPIs and loop diuretics. Further investigations are needed to identify additional factors that influence ATV exposure.<\/jats:p><\/jats:sec><\/jats:sec>","DOI":"10.1111\/bcp.14133","type":"journal-article","created":{"date-parts":[[2019,10,27]],"date-time":"2019-10-27T05:39:54Z","timestamp":1572154794000},"page":"62-74","source":"Crossref","is-referenced-by-count":13,"title":["Investigating the clinical factors and comedications associated with circulating levels of atorvastatin and its major metabolites in secondary prevention"],"prefix":"10.1111","volume":"86","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7315-679X","authenticated-orcid":false,"given":"Richard M.","family":"Turner","sequence":"first","affiliation":[{"name":"Department of Molecular &amp; Clinical Pharmacology University of Liverpool  United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vanessa","family":"Fontana","sequence":"additional","affiliation":[{"name":"Department of Molecular &amp; Clinical Pharmacology 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