{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T14:38:04Z","timestamp":1786977484826,"version":"build-2736575974"},"reference-count":30,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2022,3,28]],"date-time":"2022-03-28T00:00:00Z","timestamp":1648425600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clin Pharma and Therapeutics"],"published-print":{"date-parts":[[2022,6]]},"abstract":"<jats:p>\n                    Precision dosing strategies require accounting for between\u2010patient variability in pharmacokinetics together with subsequent pharmacodynamic differences. Liquid biopsy is a valuable new approach to diagnose disease prior to the appearance of clinical signs and symptoms, potentially circumventing invasive tissue biopsies. However, the possibility of quantitative grading of biomarkers, as opposed to simply confirming their presence or absence, is relatively new. In this study, we aimed to verify expression measurements of cytochrome P450 (CYP) enzymes and the transporter P\u2010glycoprotein (P\u2010gp) in liquid biopsy against genotype and activity phenotype (assessed by the Geneva cocktail approach) in 30 acutely ill patients with cardiovascular disease in a hospital setting. After accounting for exosomal shedding, expression in liquid biopsy correlated with activity phenotype for CYP1A2, CYP2B6, CYP2C9, CYP3A, and P\u2010gp (\n                    <jats:italic>r<\/jats:italic>\n                    \u00a0=\u00a00.44\u20130.70,\n                    <jats:italic>P<\/jats:italic>\n                    \u00a0\u2264\u00a00.05). Although genotype offered a degree of stratification, large variability (coefficient of variation (CV)) in activity (up to 157%) and expression in liquid biopsy (up to 117%) was observed within each genotype, indicating a mismatch between genotype and phenotype. Further, exosome screening revealed expression of 497 targets relevant to drug metabolism and disposition (159 enzymes and 336 transporters), as well as 20 molecular drug targets. Although there were no functional data available to correlate against these large\u2010scale measurements, assessment of disease perturbation from healthy baseline was possible. Verification of liquid biopsy against activity phenotype is important to further individualize modeling approaches that aspire to achieve precision dosing from the start of drug treatment without the need for multiple rounds of dose optimization.\n                  <\/jats:p>","DOI":"10.1002\/cpt.2576","type":"journal-article","created":{"date-parts":[[2022,3,9]],"date-time":"2022-03-09T11:59:59Z","timestamp":1646827199000},"page":"1268-1277","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":40,"title":["Liquid Biopsy for Patient Characterization in Cardiovascular Disease: Verification against Markers of Cytochrome P450 and P\u2010Glycoprotein Activities"],"prefix":"10.1111","volume":"111","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2595-5626","authenticated-orcid":false,"given":"Brahim","family":"Achour","sequence":"first","affiliation":[{"name":"Centre for Applied Pharmacokinetic Research School of Health Sciences University of Manchester Manchester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pauline","family":"Gosselin","sequence":"additional","affiliation":[{"name":"General Internal Medicine Department of Medicine Geneva University Hospitals Geneva Switzerland"},{"name":"Geneva Platelet Group Faculty of Medicine University of Geneva Geneva Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean","family":"Terrier","sequence":"additional","affiliation":[{"name":"General Internal Medicine Department of Medicine Geneva University Hospitals Geneva Switzerland"},{"name":"Geneva Platelet Group Faculty of Medicine University of Geneva Geneva Switzerland"},{"name":"Clinical Pharmacology and Toxicology Department of Anaesthesiology, Pharmacology, Intensive Care and Emergency Medicine Geneva University Hospitals Geneva Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yvonne","family":"Gloor","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology and Toxicology Department of Anaesthesiology, Pharmacology, Intensive Care and Emergency Medicine Geneva University Hospitals Geneva Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1497-3140","authenticated-orcid":false,"given":"Zubida M.","family":"Al\u2010Majdoub","sequence":"additional","affiliation":[{"name":"Centre for Applied Pharmacokinetic Research School of Health Sciences University of Manchester Manchester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1008-5223","authenticated-orcid":false,"given":"Thomas M.","family":"Polasek","sequence":"additional","affiliation":[{"name":"Certara Princeton New Jersey USA"},{"name":"Department of Clinical Pharmacology Royal Adelaide Hospital Adelaide South Australia Australia"},{"name":"Centre for Medicine Use and Safety Monash University Melbourne Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Youssef","family":"Daali","sequence":"additional","affiliation":[{"name":"Geneva Platelet Group Faculty of Medicine University of Geneva Geneva Switzerland"},{"name":"Clinical Pharmacology and Toxicology Department of Anaesthesiology, Pharmacology, Intensive Care and Emergency Medicine Geneva University Hospitals Geneva Switzerland"},{"name":"Institute of Pharmaceutical Sciences of Western Switzerland University of Geneva Geneva Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3917-844X","authenticated-orcid":false,"given":"Amin","family":"Rostami\u2010Hodjegan","sequence":"additional","affiliation":[{"name":"Centre for Applied Pharmacokinetic Research School of Health Sciences University of Manchester Manchester UK"},{"name":"Certara Princeton New Jersey USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean\u2010Luc","family":"Reny","sequence":"additional","affiliation":[{"name":"General Internal Medicine Department of Medicine Geneva University Hospitals Geneva Switzerland"},{"name":"Geneva Platelet Group Faculty of Medicine University of Geneva Geneva Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,3,28]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1080\/17512433.2018.1501271"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-pharmtox-033020-113257"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.clpt.6100406"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/clpt.2014.83"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2125.2010.03773.x"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.2102"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/bcp.13793"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0140712"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1634\/theoncologist.2019-0441"},{"key":"e_1_2_10_11_1","unstructured":"Rostami\u2010Hodjegan 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Achour B.&Rothman J.E.Methods and apparatus for quantifying protein abundance in tissues via cell free ribonucleic acids in liquid biopsy. Patent No. WO2019191297 (2021)."},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.2244"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-014-0550-8"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.2146"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.4155\/bio.13.289"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4939-9833-3_15"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/wsbm.1417"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1177\/0091270006293753"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1111\/cts.12490"},{"key":"e_1_2_10_20_1","unstructured":"US FDA.Enhancing the diversity of clinical trial populations\u2014eligibility criteria enrollment practices and trial designs guidance for industry<https:\/\/www.fda.gov\/media\/127712\/download> (2020)."},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.2056"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.1328"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.117.310782"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpba.2019.112901"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.3389\/fgene.2013.00012"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ygyno.2008.04.033"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.3892\/or.2016.5066"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1002\/gcc.21926"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.1778"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2125.2010.03799.x"},{"key":"e_1_2_10_31_1","article-title":"Clinical and molecular perspectives on inflammation\u2010mediated regulation of drug metabolism and transport","author":"Dunvald A.D.","journal-title":"Clin. 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