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Population pharmacokinetics-pharmacodynamics of fondaparinux in dialysis-dependent chronic kidney disease patients undergoing chronic renal replacement therapy

D. Michaličková, JM. Hartinger, Z. Hladinová, V. Bednářová, B. Szonowská, V. Polakovič, A. Matthios, V. Tesař, O. Slanař, EHJ. Krekels

. 2022 ; 78 (1) : 89-98. [pub] 20210819

Jazyk angličtina Země Německo

Typ dokumentu časopisecké články, pozorovací studie

Perzistentní odkaz   https://www.medvik.cz/link/bmc22011462

Grantová podpora
Project Progres Q25 Univerzita Karlova v Praze
No. SVV 260 523 Univerzita Karlova v Praze

E-zdroje Online Plný text

NLK ProQuest Central od 1997-01-01 do Před 1 rokem
CINAHL Plus with Full Text (EBSCOhost) od 2008-01-01 do Před 1 rokem
Medline Complete (EBSCOhost) od 2000-01-01 do Před 1 rokem
Nursing & Allied Health Database (ProQuest) od 1997-01-01 do Před 1 rokem
Health & Medicine (ProQuest) od 1997-01-01 do Před 1 rokem

Odkazy

PubMed 34414464
DOI 10.1007/s00228-021-03201-1
Knihovny.cz E-zdroje

PURPOSE: Data on the anti-Xa efficacy of fondaparinux in dialysis-dependent chronic kidney disease (DD-CKD) patients are scarce. This study characterizes the pharmacokinetics (PK) and pharmacodynamics (PD) of fondaparinux in DD-CKD patients undergoing renal replacement therapy (RRT), to assess dosing strategies. METHODS: A retrospective, observational study was conducted using data on anti-Xa activity (112 samples) from 12 (3 male and 9 female) DD-CKD patients (median (IQR) age 71 years (63-88), weight 73 kg (59-98.5)). Eleven patients underwent high-flux or low-flux hemodialysis (HD) and one patient underwent peritoneal dialysis. Three patients were also treated with therapeutic plasma exchange (TPE). A non-linear mixed effects analysis was performed using NONMEM 7.3.0. RESULTS: The lab-specific slope of the relationship between fondaparinux concentration and anti-Xa levels was 1.18 IU/μg. In a one-compartment model, clearance (CL) and volume of distribution (Vd) were 0.05289 L/h and 5.55 L, respectively. High-flux HD was found to increase the CL of fondaparinux 2.26 times. TPE also considerably increased CL, but the fold-change could not be accurately estimated. Low-flux HD and peritoneal dialysis did not impact PK parameters. CONCLUSIONS: Model-based simulations showed that standard dosing (2.5 mg three times weekly before HD) results in a median anti-Xa activity of 0.55 IU/mL and 0.98 IU/mL, pre- and post-low-flux HD, respectively. In patients undergoing high-flux HD, these values are approximately 27% lower. Additional caution is warranted with TPE, as this treatment can reduce anti-Xa activity even further.

Citace poskytuje Crossref.org

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