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Effect of amiodarone on apixaban exposure in patients after cardiac surgery: a population pharmacokinetic study

Aim: To investigate the effect of amiodarone on apixaban pharmacokinetics in cardiac surgery patients with postoperative atrial fibrillation. Methods: Apixaban concentrations of postoperative cardiac surgery patients with or without amiodarone therapy were quantified using liquid chromatography–tand...

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Main Authors: Morath, Benedict (Author) , Foerster, Kathrin (Author) , Chiriac, Ute (Author) , Zaradzki, Marcin (Author) , Hoppe-Tichy, Torsten (Author) , Schrey, David (Author) , Burhenne, Jürgen (Author) , Czock, David (Author) , Karck, Matthias (Author) , Haefeli, Walter E. (Author) , Wicha, Sebastian G. (Author)
Format: Article (Journal)
Language:English
Published: 05 June 2025
In: Clinical pharmacokinetics
Year: 2025, Volume: 64, Issue: 8, Pages: 1191-1201
ISSN:1179-1926
DOI:10.1007/s40262-025-01534-z
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1007/s40262-025-01534-z
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Author Notes:Benedict Morath, Kathrin I. Foerster, Ute Chiriac, Marcin Zaradzki, Torsten Hoppe-Tichy, David Schrey, Jürgen Burhenne, David Czock, Matthias Karck, Walter E. Haefeli, Sebastian G. Wicha
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Summary:Aim: To investigate the effect of amiodarone on apixaban pharmacokinetics in cardiac surgery patients with postoperative atrial fibrillation. Methods: Apixaban concentrations of postoperative cardiac surgery patients with or without amiodarone therapy were quantified using liquid chromatography–tandem mass spectrometry (LC–MS/MS) in clinical routine. A population pharmacokinetic model was built using nonlinear mixed effects modeling in NONMEM® 7.5 using first-order conditional estimation with interaction. The impact of amiodarone and creatinine clearance (CrCL) on apixaban exposure under various dosing regimens was analyzed using Simulx® (Lixoft). Results: A total of 33 patients with 76 apixaban concentrations were included. A one-compartment model best described the pharmacokinetics of apixaban with a clearance (CL/F) of 3.05 L/h, apparent volume of distribution (Vd/F) of 23.7 L, and an absorption rate constant (ka) of 0.652/h. Interindividual variability (IIV) was observed in CL/F but not in Vd/F and ka. The covariates amiodarone and CrCL were independently associated with apixaban CL/F. Under concomitant amiodarone therapy, simulations predicted an increase of 44–49% in apixaban area under the concentration–time curve (AUC), and AUC nearly doubled at CrCL 35 mL/min. A dose of 2.5 mg apixaban twice daily (b.i.d.) was identified as a potential dosing option in the CrCL range of 15–50 mL/min under amiodarone comedication. Conclusions: Concomitant amiodarone therapy reduced apixaban CL/F and increased the risk of high exposure in patients with impaired renal function. A dose of 2.5 mg apixaban b.i.d. for a CrCL range of 30–50 mL/min under concomitant amiodarone therapy was identified as a new dosing option.
Item Description:Gesehen am 12.09.2025
Physical Description:Online Resource
ISSN:1179-1926
DOI:10.1007/s40262-025-01534-z

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