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Scientific article
Open access
English

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

Published inCPT: pharmacometrics & systems pharmacology, vol. 12, no. 12, p. 1872-1883
Publication date2023-12
First online date2023-10-04
Abstract

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 [AUCtau] = 0.97 [0.96-0.99] geometric mean, 90% confidence interval, ratio predicted/observed AUCtau = 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.

eng
Keywords
  • Humans
  • Aged
  • Rivaroxaban / pharmacokinetics
  • Pyrazoles / pharmacokinetics
  • Pyridones / pharmacokinetics
  • Administration, Oral
  • Anticoagulants
Citation (ISO format)
TERRIER, Jean et al. 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. In: CPT: pharmacometrics & systems pharmacology, 2023, vol. 12, n° 12, p. 1872–1883. doi: 10.1002/psp4.13036
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ISSN of the journal2163-8306
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Creation01/04/2024 9:42:06 AM
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