Population pharmacokinetics of apixaban in a real-life hospitalized population from the OptimAT study

Article Article scientifique Article Population pharmacokinetics of apixaban in a real-life hospitalized population from the OptimAT study eng 2023-09-18 2023-10 author Gaspar Frédéric 781664 Section des sciences pharmaceutiques (FARMA) author Terrier Jean 536564 author Favre Samantha Ophélie Olivia 902361 author Gosselin Pauline 804518 author Fontana Pierre 0000-0003-1546-0774 135328 Département de médecine (DEMED) author Daali Youssef 46042 Département d'anesthésiologie, pharmacologie et soins intensifs (APSIC) author Lenoir Camille 0000-0001-6506-8629 777980 author Samer Caroline Flora 0000-0001-8178-0616 105661 Département d'anesthésiologie, pharmacologie et soins intensifs (APSIC) author Rollason Victoria 40955 Département d'anesthésiologie, pharmacologie et soins intensifs (APSIC) author Reny Jean-Luc 0000-0002-7528-7363 704339 Département de médecine (DEMED) author Csajka Chantal 657943 Section des sciences pharmaceutiques (FARMA) author Guidi Monia 762075 1541-1552 10.1002/psp4.13032 37723920 2163-8306 https://ascpt.onlinelibrary.wiley.com/doi/10.1002/psp4.13032 This study aimed to characterize apixaban pharmacokinetics (PKs) and its variability in a real-world clinical setting of hospitalized patients using a population PK (PopPK) approach. Model-based simulations helped to identify factors that affect apixaban exposure and their clinical significance. A classic stepwise strategy was applied to determine the best PopPK model for describing typical apixaban PKs in hospitalized patients from the OptimAT study (<i>n</i> = 100) and evaluating the associated variability and influencing factors. Apixaban exposure under specific conditions was assessed using the final model. A two-compartment model with first-order absorption and elimination best described the data. The developed PopPK model revealed a major role of renal function and a minor role of P-glycoprotein phenotypic (P-gp) activity in explaining apixaban variability. The final model indicated that a patient with stage 4 chronic kidney disease (creatinine clearance [CLcr] = 15–29 mL/min) would have a 45% higher drug exposure than a patient with normal renal function (CLcr >90 mL/min), with a further 12% increase if the patient was also a poor metabolizer of P-gp. A high interindividual variability in apixaban PKs was observed in a real-life setting, which was partially explained by renal function and by P-gp phenotypic activity. Target apixaban concentrations are reached under standard dosage regimens, but overexposure can rapidly occur in the presence of cumulative factors warranting the development of a predictive tool for tailoring apixaban exposure and its clinical utility in at-risk patients. Area Under Curve Humans Models, Biological Pyrazoles / pharmacokinetics Pyridones / pharmacokinetics Apixaban Pyridones Pyrazoles Dewey 615 Dewey 616 Dewey 617 Swiss National Science Foundation Automated detection of adverse drug events from older inpatients’ electronic medical records using structured data mining and natural language processing 167381 CH Programmes 56 Département de médecine 221 63 Département d'anesthésiologie, pharmacologie, soins intensifs et urgences 229 31 Section des sciences pharmaceutiques 17 false 11 Plaquettes et antithrombotiques 13 302 Groupe Desmeules Jules (pharmacologie/toxicologie) 567 1280 Pharmaco-omiques et médecine de précision 1003 319 Groupe Perrier Arnaud (Médecine interne générale, de réhabilitation et de gériatrie) 585 887 Pharmacie hospitalière et clinique CPT: pharmacometrics & systems pharmacology 12 10 df07ead7-4ee5-41da-a252-9a2de7336cab Article (Published version) Public file.pdf 787390 application/pdf CC BY-NC-4.0 8931ad2ed7dcc9c1fdc800ef485f66cc16b1b2e4927798ac74befe039e29add3 0af97684-3647-413f-bf81-0ae539b1f424 Appendix Public psp413032-sup-0001-figures1.docx 559131 application/vnd.openxmlformats-officedocument.wordprocessingml.document dad69b0416d1727948ecf764b91d65e05f21f02c54f0e2530fb0dcc9b5afdd95 openAccess Faculté de médecine / Section de médecine clinique / Département de médecine Faculté de médecine / Section de médecine clinique / Département d'anesthésiologie, pharmacologie, soins intensifs et urgences Faculté des sciences / Section des sciences pharmaceutiques

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Population pharmacokinetics of apixaban in a real-life hospitalized population from the OptimAT study	CPT: pharmacometrics & systems pharmacology			2023	144	532

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Favre, Samantha Ophélie Olivia