Population pharmacokinetics and exposure-response modeling for evinacumab in homozygous familial hypercholesterolemia.
Journal
CPT: pharmacometrics & systems pharmacology
ISSN: 2163-8306
Titre abrégé: CPT Pharmacometrics Syst Pharmacol
Pays: United States
ID NLM: 101580011
Informations de publication
Date de publication:
11 2021
11 2021
Historique:
revised:
16
08
2021
received:
20
05
2021
accepted:
22
08
2021
pubmed:
30
9
2021
medline:
5
4
2022
entrez:
29
9
2021
Statut:
ppublish
Résumé
Evinacumab, an angiopoietin-like protein 3 (ANGPTL3) inhibitor, has been shown to significantly reduce low-density lipoprotein cholesterol (LDL-C) in patients with homozygous familial hypercholesterolemia (HoFH). This work characterized the population pharmacokinetics (PK)/pharmacodynamics (PD) of evinacumab using pooled phase III clinical data. Total evinacumab PK were described by a two-compartment model with combined linear and saturable (Michaelis-Menten) elimination, and first-order absorption. At clinically relevant concentrations, plasma drug concentrations were mainly influenced by the linear clearance pathway. Although the maximum target-mediated rate of elimination (V
Identifiants
pubmed: 34585515
doi: 10.1002/psp4.12711
pmc: PMC8592514
doi:
Substances chimiques
ANGPTL3 protein, human
0
Angiopoietin-Like Protein 3
0
Angiopoietin-like Proteins
0
Antibodies, Monoclonal
0
Cholesterol, LDL
0
evinacumab
T8B2ORP1DW
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1412-1421Subventions
Organisme : Regeneron Pharmaceuticals, Inc
Informations de copyright
© 2021 The Authors. CPT: Pharmacometrics & Systems Pharmacology published by Wiley Periodicals LLC on behalf of the American Society for Clinical Pharmacology and Therapeutics.
Références
Atherosclerosis. 2016 Dec;255:128-139
pubmed: 27839699
Clin Pharmacokinet. 2019 Nov;58(11):1455-1467
pubmed: 31055792
Cardiol Young. 2002 Mar;12(2):105-12
pubmed: 12018713
N Engl J Med. 2020 Aug 20;383(8):711-720
pubmed: 32813947
Atherosclerosis. 2017 Feb;257:86-89
pubmed: 28126585
N Engl J Med. 2017 Jul 20;377(3):296-297
pubmed: 28723334
CPT Pharmacometrics Syst Pharmacol. 2016 Nov;5(11):617-624
pubmed: 27778477
Clin Pharmacokinet. 2019 Jan;58(1):101-113
pubmed: 29725996
CPT Pharmacometrics Syst Pharmacol. 2017 Sep;6(9):576-588
pubmed: 28653357
Clin Transl Sci. 2018 Nov;11(6):540-552
pubmed: 29877608
Nat Rev Endocrinol. 2017 Dec;13(12):731-739
pubmed: 28984319
Circ Res. 2020 Sep 25;127(8):1112-1114
pubmed: 32808882
Eur Heart J. 2013 Dec;34(45):3478-90a
pubmed: 23956253
Eur Heart J. 2014 Aug 21;35(32):2146-57
pubmed: 25053660
J Lipid Res. 2020 Sep;61(9):1271-1286
pubmed: 32646941
N Engl J Med. 2017 Jul 20;377(3):211-221
pubmed: 28538136
J Lipid Res. 2015 Jul;56(7):1296-307
pubmed: 25954050
Atherosclerosis. 2020 Dec;314:33-40
pubmed: 33130482
J Pharmacokinet Biopharm. 1993 Aug;21(4):457-78
pubmed: 8133465
CPT Pharmacometrics Syst Pharmacol. 2021 Nov;10(11):1412-1421
pubmed: 34585515
J Pharmacokinet Pharmacodyn. 2003 Dec;30(6):387-404
pubmed: 15000421
Circulation. 2019 Aug 6;140(6):470-486
pubmed: 31242752
N Engl J Med. 2010 Dec 2;363(23):2220-7
pubmed: 20942659
Arterioscler Thromb Vasc Biol. 2007 Feb;27(2):366-72
pubmed: 17110602