{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,5]],"date-time":"2026-09-05T01:13:29Z","timestamp":1788570809168,"version":"build-2803163510"},"reference-count":25,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2024,1,16]],"date-time":"2024-01-16T00:00:00Z","timestamp":1705363200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001711","name":"Schweizerischer Nationalfonds zur F\u00f6rderung der Wissenschaftlichen Forschung","doi-asserted-by":"publisher","award":["324730_192449"],"award-info":[{"award-number":["324730_192449"]}],"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":[[2024,4]]},"abstract":"<jats:sec><jats:title>Aims<\/jats:title><jats:p>The pharmacokinetics of doravirine has been studied in clinical trials but not in real\u2010world settings. Our study aims to characterize and identify factors influencing doravirine (a CYP3A4 substrate) pharmacokinetics in real\u2010world people with HIV (PWH).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A total of 174 doravirine concentrations measured in 146 PWH followed up in the therapeutic drug monitoring (TDM) program at the University Hospital of Lausanne (Switzerland) between 2019 and 2023 were included in the analysis. Demographic data, clinical information and comedications were recorded during the routine SHCS visits (every 3\u20136 months). Population pharmacokinetic analysis and Monte Carlo simulations to investigate the clinical significance of the covariates retained in the final model were performed using NONMEM.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>A one\u2010compartment model with first\u2010order absorption and linear elimination best described doravirine pharmacokinetics. Potent CYP3A4 inhibitors and, to a lesser extent age, were the only tested covariates to significantly impact doravirine clearance (CL). Potent CYP3A4 inhibitors reduced CL by 50%, and a 30% decrease in CL was observed in an 80\u2010year\u2010old compared with a 55\u2010year\u2010old PWH. The effect of potent CYP3A4 inhibitors was prominent, explaining 59% of between\u2010subject variability in CL. Model\u2010based simulations predicted 2.8\u2010fold and 1.6\u2010fold increases in median steady\u2010state trough and maximum doravirine concentrations, respectively, when a potent CYP3A4 inhibitor was co\u2010administered.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Our findings show that potent CYP3A4 inhibitors and age influence doravirine pharmacokinetics. However, given the good tolerability of doravirine, dosing adjustment of doravirine is probably not mandatory in those situations. TDM remains useful essentially in specific clinical situations, such as hepatic impairment, suspected nonadherence or pregnancy.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bcp.15975","type":"journal-article","created":{"date-parts":[[2023,11,23]],"date-time":"2023-11-23T16:50:04Z","timestamp":1700758204000},"page":"1058-1065","source":"Crossref","is-referenced-by-count":1,"title":["Population pharmacokinetic analysis of doravirine in real\u2010world people with HIV"],"prefix":"10.1111","volume":"90","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2305-4277","authenticated-orcid":false,"given":"Paul","family":"Thoueille","sequence":"first","affiliation":[{"name":"Service and Laboratory of Clinical Pharmacology, Department of Laboratory Medicine and Pathology Lausanne University Hospital and University of Lausanne  Lausanne Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luc","family":"Delarive","sequence":"additional","affiliation":[{"name":"Service and Laboratory of Clinical Pharmacology, Department of Laboratory Medicine and Pathology 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, Department of Medicine Lausanne University Hospital and University of Lausanne  Lausanne Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thierry","family":"Buclin","sequence":"additional","affiliation":[{"name":"Service and Laboratory of Clinical Pharmacology, Department of Laboratory Medicine and Pathology Lausanne University Hospital and University of Lausanne  Lausanne Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laurent A.","family":"Decosterd","sequence":"additional","affiliation":[{"name":"Service and Laboratory of Clinical Pharmacology, Department of Laboratory Medicine and Pathology Lausanne University Hospital and University of Lausanne  Lausanne Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catia","family":"Marzolini","sequence":"additional","affiliation":[{"name":"Service and Laboratory of Clinical Pharmacology, Department of Laboratory Medicine and Pathology Lausanne University Hospital and University of Lausanne  Lausanne Switzerland"},{"name":"Division of Infectious Diseases and Hospital Epidemiology University Hospital Basel, University of Basel  Basel Switzerland"},{"name":"Department of Molecular and Clinical Pharmacology, Institute of Translational Medicine University of Liverpool  Liverpool UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0842-927X","authenticated-orcid":false,"given":"Fran\u00e7ois R.","family":"Girardin","sequence":"additional","affiliation":[{"name":"Service and Laboratory of Clinical Pharmacology, Department of Laboratory Medicine and Pathology Lausanne University Hospital and University of Lausanne  Lausanne Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6419-9317","authenticated-orcid":false,"given":"Monia","family":"Guidi","sequence":"additional","affiliation":[{"name":"Service and Laboratory of Clinical Pharmacology, Department of Laboratory Medicine and Pathology Lausanne University Hospital and University of Lausanne  Lausanne Switzerland"},{"name":"Center for Research and Innovation in Clinical Pharmaceutical Sciences Lausanne University Hospital and University of Lausanne  Lausanne Switzerland"},{"name":"Institute of Pharmaceutical Sciences of Western Switzerland, 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":[[2024,1,16]]},"reference":[{"key":"e_1_2_10_2_1","unstructured":"European Medicines Agency.Pifeltro: EPAR\u2014Product Information. 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