Pharmacokinetics of Apixaban Among Peritoneal Dialysis Patients

Winston Wing-Shing Fung; Phyllis Mei-Shan Cheng; Jack Kit-Chung Ng; Gordon Chun-Kau Chan; Kai Ming Chow; Philip Kam-Tao Li; Cheuk Chun Szeto

doi:10.1016/j.xkme.2023.100646

Pharmacokinetics of Apixaban Among Peritoneal Dialysis Patients

Kidney Med. 2023 May 2;5(8):100646. doi: 10.1016/j.xkme.2023.100646. eCollection 2023 Aug.

Authors

Winston Wing-Shing Fung¹, Phyllis Mei-Shan Cheng¹, Jack Kit-Chung Ng¹, Gordon Chun-Kau Chan¹, Kai Ming Chow¹, Philip Kam-Tao Li¹, Cheuk Chun Szeto^{1

2}

Affiliations

¹ Department of Medicine & Therapeutics, Prince of Wales Hospital, Shatin, Hong Kong, China.
² Li Ka Shing Institute of Health Sciences (LiHS), The Chinese University of Hong Kong, Shatin, Hong Kong, China.

Abstract

Rationale & objective: The efficacy and safety profile of apixaban remains uncertain in patients receiving peritoneal dialysis (PD) despite increasing use in this population. Accordingly, we assessed the pharmacokinetics of apixaban among patients receiving PD.

Study design: A pharmacokinetics study in a single center. Patients recruited received 1 week of apixaban at 2.5 mg twice a day to reach steady state. Serial blood samples were then taken before and after the last dose for pharmacokinetics analysis of apixaban.

Setting & participants: Ten stable PD patients with atrial fibrillation in an outpatient setting.

Analytical approach/outcomes: Pharmacokinetic parameters including the area under the concentration-time curve from time 0 to 12 hours after the last dose of apixaban (AUC0-12), peak concentration, trough level, time to peak apixaban concentration, half-life, and drug clearance were analyzed.

Results: There was a wide variation in the range of apixaban concentration across the 10 patients. The AUC_0-12 for the PD group was significantly higher than those reported previously for hemodialysis patients or healthy individuals. Three patients had a supratherapeutic peak concentration whereas 2 patients had a supratherapeutic trough level as compared with the pharmacokinetic parameter in healthy individuals taking equivalent therapeutic dosage.

Limitations: Small sample size with short study duration limits the ability to ascertain the true bleeding risk and to detect any clinical outcomes. Results may be limited to Asian populations only.

Conclusions: A proportion of PD patients had supratherapeutic levels even when the reduced dosage 2.5 mg twice a day was used. Given the large interindividual variation in the drug level, therapeutic drug monitoring should be done if available. Otherwise, one should start the drug at reduced doses with caution and with more frequent clinical monitoring for any signs of bleeding.

Keywords: Apixaban; direct oral anticoagulant; drug monitoring; peritoneal dialysis; pharmacokinetics.