Apixaban and rivaroxaban's physiologically-based pharmacokinetic model validation in hospitalized patients: A first step for larger use of a priori modeling approach at bed side

Article Article scientifique Article Apixaban and rivaroxaban's physiologically-based pharmacokinetic model validation in hospitalized patients: A first step for larger use of a priori modeling approach at bed side eng 2023-10-04 2023-12 author Terrier Jean 0000-0002-5878-4878 Division of General Internal Medicine, Geneva University Hospitals, Geneva, Switzerland.,Geneva Platelet Group, Faculty of Medicine, University of Geneva, Geneva, Switzerland.,Clinical Pharmacology and Toxicology Service, Anesthesiology, Pharmacology and Intensive Care Department, Geneva University Hospitals, Geneva, Switzerland. 536564 author Gaspar Frédéric 0000-0002-0225-7294 Center for Research and Innovation in Clinical Pharmaceutical Sciences, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.,School of Pharmaceutical Sciences, University of Geneva, Geneva, Switzerland.,Institute of Pharmaceutical Sciences of Western Switzerland, University of Geneva, University of Lausanne, Geneva, Lausanne, Switzerland.,Service of Clinical Pharmacology, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland. 781664 Section des sciences pharmaceutiques (FARMA) author Gosselin Pauline Division of General Internal Medicine, Geneva University Hospitals, Geneva, Switzerland. 804518 author Raboud Olivier Thanonchaï Center for Research and Innovation in Clinical Pharmaceutical Sciences, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.,School of Pharmaceutical Sciences, University of Geneva, Geneva, Switzerland.,Institute of Pharmaceutical Sciences of Western Switzerland, University of Geneva, University of Lausanne, Geneva, Lausanne, Switzerland.,Service of Clinical Pharmacology, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland. 900306 author Lenoir Camille 0000-0001-6506-8629 Clinical Pharmacology and Toxicology Service, Anesthesiology, Pharmacology and Intensive Care Department, Geneva University Hospitals, Geneva, Switzerland. 777980 author Rollason Victoria Clinical Pharmacology and Toxicology Service, Anesthesiology, Pharmacology and Intensive Care Department, Geneva University Hospitals, Geneva, Switzerland. 40955 Département d'anesthésiologie, pharmacologie et soins intensifs (APSIC) author Csajka Chantal School of Pharmaceutical Sciences, University of Geneva, Geneva, Switzerland.,Institute of Pharmaceutical Sciences of Western Switzerland, University of Geneva, University of Lausanne, Geneva, Lausanne, Switzerland.,Service of Clinical Pharmacology, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland. 657943 Section des sciences pharmaceutiques (FARMA) author Samer Caroline Flora 0000-0001-8178-0616 Clinical Pharmacology and Toxicology Service, Anesthesiology, Pharmacology and Intensive Care Department, Geneva University Hospitals, Geneva, Switzerland.,School of Pharmaceutical Sciences, University of Geneva, Geneva, Switzerland. 105661 Département d'anesthésiologie, pharmacologie et soins intensifs (APSIC) author Fontana Pierre 0000-0003-1546-0774 Geneva Platelet Group, Faculty of Medicine, University of Geneva, Geneva, Switzerland.,Division of Angiology and Haemostasis, Geneva University Hospitals, Geneva, Switzerland. 135328 Département de médecine (DEMED) author Daali Youssef Geneva Platelet Group, Faculty of Medicine, University of Geneva, Geneva, Switzerland.,Clinical Pharmacology and Toxicology Service, Anesthesiology, Pharmacology and Intensive Care Department, Geneva University Hospitals, Geneva, Switzerland. 46042 Département d'anesthésiologie, pharmacologie et soins intensifs (APSIC) author Reny Jean-Luc 0000-0002-7528-7363 Division of General Internal Medicine, Geneva University Hospitals, Geneva, Switzerland.,Geneva Platelet Group, Faculty of Medicine, University of Geneva, Geneva, Switzerland. 704339 Département de médecine (DEMED) OptimAT study group 1872-1883 10.1002/psp4.13036 37794718 2163-8306 PMC10725260 https://ascpt.onlinelibrary.wiley.com/doi/10.1002/psp4.13036 When used in real-world conditions, substantial interindividual variations in direct oral anticoagulant (DOAC) plasma concentrations are observed for a given dose, leading to a risk of over- or under-exposure and clinically significant adverse events. Physiologically-based pharmacokinetic (PBPK) models could help physicians to tailor DOAC prescriptions in vulnerable patient populations, such as those in the hospital setting. The present study aims to validate prospectively PBPK models for rivaroxaban and apixaban in a large cohort of elderly, polymorbid, and hospitalized patients. In using a model of geriatric population integrating appropriate physiological parameters into models first optimized with healthy volunteer data, observed plasma concentration collected in hospitalized patients on apixaban (n = 100) and rivaroxaban (n = 100) were adequately predicted (ratio predicted/observed area under the concentration curve for a dosing interval [AUC<sub>tau</sub>] = 0.97 [0.96-0.99] geometric mean, 90% confidence interval, ratio predicted/observed AUC<sub>tau</sub> = 1.03 [1.02-1.05]) for apixaban and rivaroxaban, respectively. Validation of the present PBPK models for rivaroxaban and apixaban in in-patients represent an additional step toward the feasibility of bedside use. Humans Aged Rivaroxaban / pharmacokinetics Pyrazoles / pharmacokinetics Pyridones / pharmacokinetics Administration, Oral Anticoagulants Dewey 615 Dewey 616 Dewey 617 56 Département de médecine 221 31 Section des sciences pharmaceutiques 17 63 Département d'anesthésiologie, pharmacologie, soins intensifs et urgences 229 false 11 Plaquettes et antithrombotiques 13 887 Pharmacie hospitalière et clinique 1280 Pharmaco-omiques et médecine de précision 1003 CPT: pharmacometrics & systems pharmacology 12 12 f4adad68-9d7f-471c-a925-90c70c4eae7d Article (Published version) Public file.pdf 1862511 application/pdf CC BY-NC-ND-4.0 68794bf34a93c7b60e89dd3ec4489d36391720dca1170b370d464cd0c8bad7bc 7445b988-16bf-4f52-899d-f042bed77295 Appendix Public PSP4-12-1872-s010.docx 34535 application/vnd.openxmlformats-officedocument.wordprocessingml.document 878bc64672a5ed5ee1ccbccad5bdcd6f659a8d072acc64d84099c72c21cf3b40 a9a2c20e-b5c1-4f2e-be3c-39f81a9ca224 Appendix Public PSP4-12-1872-s003.docx 26379 application/vnd.openxmlformats-officedocument.wordprocessingml.document f286f1bdb6ecfcf5fd2d0864ff7f62ee127cdbf0a1a5b0573a82c66912b3e7f8 c05aca54-f862-4faa-ae2e-dd177e7f5263 Appendix Public PSP4-12-1872-s004.docx 18982 application/vnd.openxmlformats-officedocument.wordprocessingml.document 26da3272a75950220a3ebf71258f1eb3ed71ae5d7234616e8483ced714a43282 a12fc96d-272e-47a6-b26e-8e4dc8a8e909 Appendix Public PSP4-12-1872-s002.docx 18996 application/vnd.openxmlformats-officedocument.wordprocessingml.document 6d3647e82a97826a8f237e8cbf62cbd1199afc24f456e2b292546640d952003c 1139a7ff-046b-4ae9-a0fd-fce1deb62c92 Appendix Public PSP4-12-1872-s005.docx 20508 application/vnd.openxmlformats-officedocument.wordprocessingml.document 0064b8320a919db4383c58e300e74eaeb5a6ce930e51828c52a2e2b265deda14 6cae9dc2-acc6-410a-be9f-680ac74e070b Appendix Public psp413036-sup-0006-figures1.jpg 38071 image/jpeg 39a9e8d7e1fb353780dfda211076fbfccf49fbd6a01b1e88bf4fa06efee7c136 e84ff5f8-29e5-44da-ad31-0d6e1dc507e4 Appendix Public psp413036-sup-0007-figures2.jpg 76543 image/jpeg ba6a92257cb2efc1e84fe754df1419966297deb2bcdbb2255bbb320ac695eb91 54764250-0af5-40f3-883e-a7dcb69273e7 Appendix Public psp413036-sup-0008-figures3.jpg 55920 image/jpeg a101d552804452ea722f0e0c715cb888cc20621eb4b0b404435ce4b9c67e6553 ef4c4a67-6bd8-4983-8ebc-9a58dd593860 Appendix Public psp413036-sup-0009-figures4.jpg 61764 image/jpeg f63a08cf025e8cc35a2d54d47979e617a7bf9275f506206f702be52f1e27b721 dafc995f-ec7c-499c-b341-4d9a0173c664 Appendix Public psp413036-sup-0010-figures5.jpg 78275 image/jpeg e1e0ca7b8bafc98e0f1f5a0b896cd1ef5b534874fe85774fac6a7b54c0db1bcf 79594423-9615-4929-9f05-6ec6da87b0d6 Appendix Public psp413036-sup-0011-figures6.jpg 60927 image/jpeg f7c2d03ff3a3cd86820f30f71cde7d5c8cdf0271549a5089e7882a02fac127bf openAccess Faculté de médecine / Section de médecine clinique / Département de médecine Faculté des sciences / Section des sciences pharmaceutiques Faculté de médecine / Section de médecine clinique / Département d'anesthésiologie, pharmacologie, soins intensifs et urgences

Title	Published in	Access level	OA Policy	Year	Views	Downloads

Apixaban and rivaroxaban's physiologically-based pharmacokinetic model validation in hospitalized patients: A first step for larger use of a priori modeling approach at bed side	CPT: pharmacometrics & systems pharmacology			2023	149	544

Archive ouverte UNIGE

Raboud, Olivier Thanonchaï