Population pharmacokinetics-pharmacodynamics of fondaparinux in dialysis-dependent chronic kidney disease patients undergoing chronic renal replacement therapy.
Fondaparinux
Hemodialysis
Peritoneal dialysis
Population pharmacokinetics-pharmacodynamics
Therapeutic plasma exchange
Journal
European journal of clinical pharmacology
ISSN: 1432-1041
Titre abrégé: Eur J Clin Pharmacol
Pays: Germany
ID NLM: 1256165
Informations de publication
Date de publication:
Jan 2022
Jan 2022
Historique:
received:
29
04
2021
accepted:
12
08
2021
pubmed:
21
8
2021
medline:
26
2
2022
entrez:
20
8
2021
Statut:
ppublish
Résumé
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. 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. 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. 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.
Identifiants
pubmed: 34414464
doi: 10.1007/s00228-021-03201-1
pii: 10.1007/s00228-021-03201-1
doi:
Substances chimiques
Factor Xa Inhibitors
0
Fondaparinux
J177FOW5JL
Types de publication
Journal Article
Observational Study
Langues
eng
Sous-ensembles de citation
IM
Pagination
89-98Subventions
Organisme : Univerzita Karlova v Praze
ID : Project Progres Q25
Organisme : Univerzita Karlova v Praze
ID : No. SVV 260 523
Commentaires et corrections
Type : ErratumIn
Informations de copyright
© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.
Références
Daugirdas J, Blake P, Ing T (2015) Handbook of dialysis. Wolters Kluwer
Haase M, Bellomo R, Rocktaeschel J, Ziemer S, Kiesewetter H, Morgera S, Neumayer HH (2005) Use of fondaparinux (ARIXTRA) in a dialysis patient with symptomatic heparin-induced thrombocytopaenia type II. Nephrol Dial Transplant 20(2):444–446. https://doi.org/10.1093/ndt/gfh544
doi: 10.1093/ndt/gfh544
pubmed: 15673695
Brown P, Jay R, Fox A, Oliver M (2013) Chronic fondaparinux use in a hemodialysis patient with heparin-induced thrombocytopenia type II and extracorporeal circuit thrombosis-a case report and review of the literature. Hemodial Int 17(3):444–449. https://doi.org/10.1111/hdi.12003
doi: 10.1111/hdi.12003
pubmed: 23216938
Taskapan H, Karahan D, Kuku I, Koc S (2010) Heparin-induced thrombocytopenia as a cause of deep venous thrombosis: effectiveness of fondaparinux in dialysis patients. Turkish Nephrology Dialysis Transplantation 19:55–57. https://doi.org/10.5262/tndt.2010.1001.09
doi: 10.5262/tndt.2010.1001.09
European Medicines Agency (2021) ( https://www.ema.europa.eu/en/medicines/human/EPAR/arixtra#product-information-section , accessed 06/23/2021) Arixtra: Summary of Product Characteristics
Speeckaert MM, Devreese KM, Vanholder RC, Dhondt A (2013) Fondaparinux as an alternative to vitamin K antagonists in haemodialysis patients. Nephrol Dial Transplant 28(12):3090–3095. https://doi.org/10.1093/ndt/gft293
doi: 10.1093/ndt/gft293
pubmed: 24021678
Mahieu E, Claes K, Jacquemin M, Evenepoel P, Op De Beek K, Bogaert AM, Kuypers D, Verhamme P, Meijers B (2013) Anticoagulation with fondaparinux for hemodiafiltration in patients with heparin-induced thrombocytopenia: dose-finding study and safety evaluation. Artif Organs 37(5):482–487. https://doi.org/10.1111/aor.12002
doi: 10.1111/aor.12002
pubmed: 23461610
Hartinger JM, Svobodová A, Malíková I, Šachl R, Slanař O (2020) Effective use of fondaparinux in patient with unresponsiveness to nadroparin. J Clin Pharm Ther. https://doi.org/10.1111/jcpt.13328
doi: 10.1111/jcpt.13328
pubmed: 33277918
Kalicki RM, Aregger F, Alberio L, Lämmle B, Frey FJ, Uehlinger DE (2007) Use of the pentasaccharide fondaparinux as an anticoagulant during haemodialysis. Thromb Haemost 98(6):1200–1207. https://doi.org/10.1160/th07-07-0444
doi: 10.1160/th07-07-0444
pubmed: 18064314
Lindbom L, Pihlgren P, Jonsson EN (2005) PsN-Toolkit–a collection of computer intensive statistical methods for non-linear mixed effect modeling using NONMEM. Comput Methods Prog Biomed 79(3):241–257. https://doi.org/10.1016/j.cmpb.2005.04.005
doi: 10.1016/j.cmpb.2005.04.005
pubmed: 16023764
Lindbom L, Ribbing J, Jonsson EN (2004) Perl-speaks-NONMEM (PsN)–a Perl module for NONMEM related programming. Comput Methods Prog Biomed 75(2):85–94. https://doi.org/10.1016/j.cmpb.2003.11.003
doi: 10.1016/j.cmpb.2003.11.003
pubmed: 15212851
Keizer RJ, van Benten M, Beijnen JH, Schellens JH, Huitema AD (2011) Pirana and PCluster: a modeling environment and cluster infrastructure for NONMEM. Comput Methods Prog Biomed 101(1):72–79. https://doi.org/10.1016/j.cmpb.2010.04.018
doi: 10.1016/j.cmpb.2010.04.018
pubmed: 20627442
Donat F, Duret JP, Santoni A, Cariou R, Necciari J, Magnani H, de Greef R (2002) The pharmacokinetics of fondaparinux sodium in healthy volunteers. Clin Pharmacokinet 41(Suppl 2):1–9. https://doi.org/10.2165/00003088-200241002-00001
doi: 10.2165/00003088-200241002-00001
pubmed: 12383039
Comets E, Brendel K, Mentré F (2008) Computing normalised prediction distribution errors to evaluate nonlinear mixed-effect models: the npde add-on package for R. Comput Methods Prog Biomed 90(2):154–166
doi: 10.1016/j.cmpb.2007.12.002
De Cock RF, Piana C, Krekels EH, Danhof M, Allegaert K, Knibbe CA (2011) The role of population PK–PD modelling in paediatric clinical research. Eur J Clin Pharmacol 67(1):5–16
doi: 10.1007/s00228-009-0782-9
Paolucci F, Claviés MC, Donat F, Necciari J (2002) Fondaparinux sodium mechanism of action: identification of specific binding to purified and human plasma-derived proteins. Clin Pharmacokinet 41(Suppl 2):11–18. https://doi.org/10.2165/00003088-200241002-00002
doi: 10.2165/00003088-200241002-00002
pubmed: 12383040
Cope J, Bushwitz J, An G, Antigua A, Patel A, Zumberg M (2015) Clinical experience with prophylactic fondaparinux in critically ill patients with moderate to severe renal impairment or renal failure requiring renal replacement therapy. Ann Pharmacother 49(3):270–277. https://doi.org/10.1177/1060028014563325
doi: 10.1177/1060028014563325
pubmed: 25515864
Delavenne X, Zufferey P, Nguyen P, Rosencher N, Samama CM, Bazzoli C, Mismetti P, Laporte S (2012) Pharmacokinetics of fondaparinux 1.5 mg once daily in a real-world cohort of patients with renal impairment undergoing major orthopaedic surgery. Eur J Clin Pharmacol 68 (10):1403–1410. https://doi.org/10.1007/s00228-012-1263-0
Cheng CW, Hendrickson JE, Tormey CA, Sidhu D (2017) Therapeutic plasma exchange and its impact on drug levels: an ACLPS critical review. Am J Clin Pathol 148(3):190–198. https://doi.org/10.1093/ajcp/aqx056
doi: 10.1093/ajcp/aqx056
pubmed: 28821193
Turpie A (2004) Fondaparinux: a factor Xa inhibitor for antithrombotic therapy. Expert Opin Pharmacother 5:1373–1384. https://doi.org/10.1517/14656566.5.6.1373
doi: 10.1517/14656566.5.6.1373
pubmed: 15163281
Ho G, Leblanc K, Selby R, Richardson R, Hladunewich M, Battistella M (2013) Use of fondaparinux for circuit patency in hemodialysis patients. Am J Kidney Dis 61(3):525–526. https://doi.org/10.1053/j.ajkd.2012.09.015
doi: 10.1053/j.ajkd.2012.09.015
pubmed: 23157936
Sombolos KI, Fragia TK, Gionanlis LC, Veneti PE, Bamichas GI, Fragidis SK, Georgoulis IE, Natse TA (2008) Use of fondaparinux as an anticoagulant during hemodialysis: a preliminary study. Int J Clin Pharmacol Ther 46(4):198–203
doi: 10.5414/CPP46198