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Scientific article
Open access
English

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

Published inCPT: pharmacometrics & systems pharmacology, vol. 12, no. 10, p. 1541-1552
Publication date2023-10
First online date2023-09-18
Abstract

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 (n = 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.

eng
Keywords
  • Area Under Curve
  • Humans
  • Models, Biological
  • Pyrazoles / pharmacokinetics
  • Pyridones / pharmacokinetics
  • Apixaban
  • Pyridones
  • Pyrazoles
Citation (ISO format)
GASPAR, Frédéric et al. Population pharmacokinetics of apixaban in a real-life hospitalized population from the OptimAT study. In: CPT: pharmacometrics & systems pharmacology, 2023, vol. 12, n° 10, p. 1541–1552. doi: 10.1002/psp4.13032
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ISSN of the journal2163-8306
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Creation01/09/2024 5:14:12 PM
First validation04/15/2024 10:41:14 AM
Update time04/15/2024 10:41:14 AM
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