{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T11:59:19Z","timestamp":1785412759890,"version":"3.56.0"},"reference-count":68,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2019,7,7]],"date-time":"2019-07-07T00:00:00Z","timestamp":1562457600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001711","name":"Schweizerischer Nationalfonds zur F\u00f6rderung der Wissenschaftlichen Forschung","doi-asserted-by":"publisher","award":["324730\u2010165956"],"award-info":[{"award-number":["324730\u2010165956"]}],"id":[{"id":"10.13039\/501100001711","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brit J Clinical Pharma"],"published-print":{"date-parts":[[2019,9]]},"abstract":"<jats:sec><jats:title>Aims<\/jats:title><jats:p>The aims of this study were to characterize escitalopram pharmacokinetic profile, to identify factors influencing drug exposure, notably drug\u2013drug interactions with antiretrovirals, and to simulate expected exposure under standard dosage regimen.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A population pharmacokinetic analysis was performed using NONMEM. A total of 159 plasma concentration measurements were obtained from 39 human immunodeficiency virus (HIV)\u2010infected and 71 uninfected psychiatric patients. The influence of age, weight, sex, HIV and psychiatric cohorts, racemic citalopram treatment, and comedications on oral clearance was examined. Simulations served to calculate the percentage of patients expected to be under\u2010 or over\u2010exposed, considering established therapeutic targets (15\u201380\u00a0ng\/mL).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>A 1\u2010compartment model with first\u2010order absorption and elimination described the data adequately. The average escitalopram clearance and volume of distribution were 23.1\u00a0L\/h (interindividual variability 51%), and 920\u00a0L, respectively. Escitalopram disposition did not differ between HIV\u2010infected and uninfected patients, and was not affected by antiretroviral treatments. Coadministration of at least 1 proton\u2010pump inhibitor (CYP2C19 inhibitor) modestly influenced escitalopram elimination (clearance decreased by 19%), with limited clinical relevance. Model\u2010based simulations showed that, under a standard regimen of 10\u00a0mg once daily, a significant proportion of patients (56%) might be under\u2010exposed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The variability in escitalopram disposition is large and poorly explained by demographic, clinical and environmental covariates, thus suggesting a role for dosage individualization based on therapeutic drug monitoring in case of poor clinical response. Escitalopram disposition is modestly impacted by comedications and therefore no a priori dosage adjustments are needed in patients receiving antiretroviral treatments, including boosted regimens.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bcp.13994","type":"journal-article","created":{"date-parts":[[2019,5,30]],"date-time":"2019-05-30T00:19:06Z","timestamp":1559175546000},"page":"2022-2032","source":"Crossref","is-referenced-by-count":11,"title":["Escitalopram population pharmacokinetics in people living with human immunodeficiency virus and in the psychiatric population: Drug\u2013drug interactions and probability of target attainment"],"prefix":"10.1111","volume":"85","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9114-7793","authenticated-orcid":false,"given":"Perrine","family":"Courlet","sequence":"first","affiliation":[{"name":"Service of Clinical Pharmacology Lausanne University Hospital and University of Lausanne  Lausanne Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monia","family":"Guidi","sequence":"additional","affiliation":[{"name":"Service of Clinical Pharmacology Lausanne University Hospital and University of Lausanne  Lausanne Switzerland"},{"name":"School of Pharmaceutical Sciences, University of Geneva University of Lausanne  Geneva Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana\u00efs","family":"Glatard","sequence":"additional","affiliation":[{"name":"Service of Clinical Pharmacology Lausanne University Hospital and University of Lausanne  Lausanne Switzerland"},{"name":"Unit of Pharmacogenetics and Clinical Psychopharmacology, Centre for Psychiatric Neuroscience, Department of Psychiatry, Hospital of Cery Lausanne University Hospital and University of Lausanne  Prilly Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susana","family":"Alves Saldanha","sequence":"additional","affiliation":[{"name":"Service of Clinical Pharmacology Lausanne University Hospital and University of Lausanne  Lausanne Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthias","family":"Cavassini","sequence":"additional","affiliation":[{"name":"Service of Infectious Diseases Lausanne University Hospital and University of Lausanne  Lausanne Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thierry","family":"Buclin","sequence":"additional","affiliation":[{"name":"Service of Clinical Pharmacology Lausanne University Hospital and University of Lausanne  Lausanne Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catia","family":"Marzolini","sequence":"additional","affiliation":[{"name":"Departments of Medicine and Clinical Research University Hospital of Basel and University of Basel  Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5439-0230","authenticated-orcid":false,"given":"Chin B.","family":"Eap","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences, University of Geneva University of Lausanne  Geneva Switzerland"},{"name":"Unit of Pharmacogenetics and Clinical Psychopharmacology, Centre for Psychiatric Neuroscience, Department of Psychiatry, Hospital of Cery Lausanne University Hospital and University of Lausanne  Prilly Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9840-1325","authenticated-orcid":false,"given":"Laurent A.","family":"Decosterd","sequence":"additional","affiliation":[{"name":"Service of Clinical Pharmacology Lausanne University Hospital and University of Lausanne  Lausanne Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0660-082X","authenticated-orcid":false,"given":"Chantal","family":"Csajka","sequence":"additional","affiliation":[{"name":"Service of Clinical Pharmacology Lausanne University Hospital and University of Lausanne  Lausanne Switzerland"},{"name":"School of Pharmaceutical Sciences, University of Geneva University of Lausanne  Geneva Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"the Swiss HIV Cohort Study","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,7,7]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1176\/appi.ajp.158.5.725"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1080\/09540121.2010.498860"},{"issue":"10","key":"e_1_2_10_4_1","first-page":"WC01","article-title":"Prevalence of depression in people living with HIV\/AIDS undergoing ART and factors associated with it","volume":"8","author":"Bhatia MS","year":"2014","journal-title":"J Clin Diagn Res"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1097\/00126334-200212153-00010"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9343(03)00093-7"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1345\/aph.1E248"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF01244820"},{"key":"e_1_2_10_9_1","unstructured":"DrewesP ThijssenI MengelH.A single\u2010dose cross\u2010over pharmacokinetic study comparing racemic citalopram (40 mg) with the S\u2010enantiomer of citalopram (escitalopram 20 mg) in healthy male volunteers. Annual Meeting of the New clinical Data Evaluation Unit; May 29\u2013June 1; Phoenix USA.2001."},{"key":"e_1_2_10_10_1","unstructured":"Lundbeck.Information de base Cipralex2006. Available from:http:\/\/www.cipralex.ch\/pdf\/basis_f.pdf. Accessed December 11 2018."},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1520-636X(1997)9:7<686::AID-CHIR9>3.0.CO;2-5"},{"key":"e_1_2_10_12_1","unstructured":"Swissmedic.Information Sur le m\u00e9dicament. [Available from:http:\/\/www.swissmedicinfo.ch\/. Accessed December 6 2017."},{"issue":"8","key":"e_1_2_10_13_1","first-page":"1102","article-title":"Escitalopram (S\u2010citalopram) and its metabolites in vitro: cytochromes mediating biotransformation, inhibitory effects, and comparison to R\u2010citalopram","volume":"29","author":"Moltke LL","year":"2001","journal-title":"Drug Metab Dispos"},{"issue":"1","key":"e_1_2_10_14_1","first-page":"9","article-title":"Consensus guidelines for therapeutic drug monitoring in neuropsychopharmacology: update 2017","volume":"51","author":"Hiemke C","year":"2018","journal-title":"Pharmacopsychiatry"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1017\/S1461145706007486"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1176\/appi.ajp.161.5.826"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1503\/jpn.130055"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1111\/bcp.12040"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2125.2005.02546.x"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2125.2011.04091.x"},{"key":"e_1_2_10_21_1","unstructured":"Food and Drug Administration.FDA drug safety communication: revised recommendations for Celexa (citalopram hydrobromide) related to a potential risk of abnormal heart rhythms with high doses.2012."},{"key":"e_1_2_10_22_1","unstructured":"CredibleMeds.University of Arizona centres for Education & Research on therapeutics (AZCERT). [Available from:https:\/\/www.crediblemeds.org\/. Accessed December 7 2017."},{"key":"e_1_2_10_23_1","unstructured":"Citalopram and escitalopram: QT interval prolongation. New maximum daily dose restrictions (including in elderly patients) contraindications and warnings. Available from:https:\/\/www.gov.uk\/drug\u2010safety\u2010update\/citalopram\u2010and\u2010escitalopram\u2010qt\u2010interval\u2010prolongation (2011). Accessed February 16 2018."},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamapsychiatry.2013.187"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jchromb.2011.12.028"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2008.09.010"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-0030-1254106"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmpb.2005.04.005"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmpb.2010.04.018"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10928-015-9457-6"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1177\/0091270009337946"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1177\/0091270008327538"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.2165\/00003088-200746040-00002"},{"key":"e_1_2_10_34_1","unstructured":"ShinK KimE KimS et al.Population pharmacokinetics and pharmacodynamics of escitalopram in healthy volunteers. Annual Meeting of the Population Approach Group in Europe; Venice2012."},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1038\/clpt.2008.302"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.1124\/dmd.107.018747"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0149-2918(03)80076-0"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40262-013-0056-7"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.1097\/FTD.0000000000000101"},{"key":"e_1_2_10_40_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2125.2005.02423.x"},{"key":"e_1_2_10_41_1","doi-asserted-by":"publisher","DOI":"10.1124\/dmd.113.051722"},{"key":"e_1_2_10_42_1","unstructured":"Service de pharmacologie et toxicologie cliniques H\u00f4pitaux Universitaires de Gen\u00e8ve. Interactions m\u00e9dicamenteuses cytochromes P450 et P\u2010glycoprot\u00e9ine (Pgp). Available from:https:\/\/www.hug\u2010ge.ch\/sites\/interhug\/files\/structures\/pharmacologie_et_toxicologie_cliniques\/a5_cytochromes_6_2.pdf. Accessed August 7 2017."},{"key":"e_1_2_10_43_1","unstructured":"Food and Drug Administration.Drug development and drug interactions: table of substrates inhibitors and inducers. Available from:https:\/\/www.fda.gov\/drugs\/developmentapprovalprocess\/developmentresources\/druginteractionslabeling\/ucm093664.htm. Accessed December 20 2017."},{"key":"e_1_2_10_44_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF01060893"},{"key":"e_1_2_10_45_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkx1121"},{"key":"e_1_2_10_46_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.13877"},{"key":"e_1_2_10_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pnpbp.2005.06.001"},{"key":"e_1_2_10_48_1","doi-asserted-by":"publisher","DOI":"10.1097\/00007691-200304000-00007"},{"key":"e_1_2_10_49_1","doi-asserted-by":"publisher","DOI":"10.1177\/0091270004269647"},{"key":"e_1_2_10_50_1","doi-asserted-by":"publisher","DOI":"10.1177\/0091270005280860"},{"key":"e_1_2_10_51_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.clpt.6100291"},{"key":"e_1_2_10_52_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40262-014-0162-1"},{"key":"e_1_2_10_53_1","doi-asserted-by":"publisher","DOI":"10.1111\/bcp.12348"},{"key":"e_1_2_10_54_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2125.2010.03649.x"},{"key":"e_1_2_10_55_1","unstructured":"TodM GoutelleS BourguignonL BleyzacN.DDI\u2010predictor. Available from:https:\/\/www.ddi\u2010predictor.org\/. Accessed December 7 2017."},{"key":"e_1_2_10_56_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.f288"},{"key":"e_1_2_10_57_1","doi-asserted-by":"publisher","DOI":"10.1097\/YIC.0000000000000124"},{"key":"e_1_2_10_58_1","doi-asserted-by":"publisher","DOI":"10.1111\/bcp.12223"},{"key":"e_1_2_10_59_1","unstructured":"European Medicine Agency.Pharmacovigilance working party (PhVWP). Escitalopram \u2013 risk of QT interval prolongation.2011. Available from:https:\/\/www.ema.europa.eu\/documents\/report\/monthly\u2010report\u2010pharmacovigilance\u2010working\u2010party\u2010phvwp\u2010november\u20102011\u2010plenary\u2010meeting_en.pdf. Accessed October 25 2018."},{"key":"e_1_2_10_60_1","unstructured":"Medicines and Healthcare products Regulatory Agency.Citalopram and escitalopram: QT interval prolongation.2011. Available from:https:\/\/www.gov.uk\/drug\u2010safety\u2010update\/citalopram\u2010and\u2010escitalopram\u2010qt\u2010interval\u2010prolongation. Accessed October 25 2018."},{"key":"e_1_2_10_61_1","unstructured":"US Food and Drug Administration.FDA drug safety communication: revised recommendations for Celexa (citalopram hydrobromide) related to a potential risk of abnormal heart rhythms with high doses.2012. Available from:https:\/\/www.fda.gov\/Drugs\/DrugSafety\/ucm297391.htm. Accessed October 25 2018."},{"key":"e_1_2_10_62_1","doi-asserted-by":"publisher","DOI":"10.1080\/15622975.2018.1500032"},{"key":"e_1_2_10_63_1","doi-asserted-by":"publisher","DOI":"10.2165\/00003088-199936040-00004"},{"key":"e_1_2_10_64_1","doi-asserted-by":"publisher","DOI":"10.1592\/phco.21.2.163.34101"},{"key":"e_1_2_10_65_1","doi-asserted-by":"publisher","DOI":"10.1097\/QAD.0b013e32835a11ba"},{"key":"e_1_2_10_66_1","doi-asserted-by":"publisher","DOI":"10.1038\/npp.2013.120"},{"key":"e_1_2_10_67_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-244X-11-42"},{"key":"e_1_2_10_68_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.690"},{"key":"e_1_2_10_69_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2125.2003.01874.x"}],"container-title":["British Journal of Clinical Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fbcp.13994","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/bcp.13994","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/bcp.13994","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/bcp.13994","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,10]],"date-time":"2023-09-10T01:31:40Z","timestamp":1694309500000},"score":1,"resource":{"primary":{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/10.1111\/bcp.13994"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,7,7]]},"references-count":68,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2019,9]]}},"alternative-id":["10.1111\/bcp.13994"],"URL":"https:\/\/doi.org\/10.1111\/bcp.13994","archive":["Portico"],"relation":{},"ISSN":["0306-5251","1365-2125"],"issn-type":[{"value":"0306-5251","type":"print"},{"value":"1365-2125","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,7,7]]}}}