The association between anti-insulin aspart antibodies and the pharmacokinetic and pharmacodynamic characteristics of fast-acting insulin aspart in children and adolescents with type 1 diabetes.
adolescents
children
insulin antibodies
pharmacodynamics
pharmacokinetics
Journal
Pediatric diabetes
ISSN: 1399-5448
Titre abrégé: Pediatr Diabetes
Pays: Denmark
ID NLM: 100939345
Informations de publication
Date de publication:
08 2020
08 2020
Historique:
received:
10
12
2019
revised:
06
03
2020
accepted:
14
04
2020
pubmed:
20
4
2020
medline:
15
7
2021
entrez:
20
4
2020
Statut:
ppublish
Résumé
Fast-acting insulin aspart (faster aspart) is a novel formulation of insulin aspart (IAsp) ensuring ultrafast absorption and effect. To compare the pharmacokinetics between faster aspart and IAsp, based on free or total IAsp measurement, and investigate the association between anti-IAsp antibodies and faster aspart and IAsp pharmacological properties in children and adolescents with type 1 diabetes (T1D). In a randomized, two-period crossover trial, 12 children, 16 adolescents, and 15 adults (6-11, 12-17, and 18-64 years) received 0.2 U/kg double-blindsingle-dose subcutaneous faster aspart or IAsp followed by a standardized liquid meal test. Across age groups, the pharmacokinetic profile was left-shifted including greater early exposure for faster aspart vs IAsp irrespective of free or total IAsp assay. Onset of appearance occurred 2.4 to 5.0 minutes (free) or 1.8 to 3.0 minutes (total) earlier for faster aspart vs IAsp (P < .05). Treatment ratios (faster aspart/IAsp) for 0 to 30 minutes IAsp exposure were 1.60 to 2.11 and 1.62 to 1.96, respectively (children, free: P = .062; otherwise P < .05). The ratio of free/total IAsp for overall exposure (AUC In children and adolescents with T1D, faster aspart provides ultrafast pharmacokinetics irrespective of free or total IAsp assay. Elevated anti-IAsp antibodies are associated with higher total IAsp concentration, but do not impact faster aspart and IAsp glucose-lowering effect.
Sections du résumé
BACKGROUND
Fast-acting insulin aspart (faster aspart) is a novel formulation of insulin aspart (IAsp) ensuring ultrafast absorption and effect.
AIM
To compare the pharmacokinetics between faster aspart and IAsp, based on free or total IAsp measurement, and investigate the association between anti-IAsp antibodies and faster aspart and IAsp pharmacological properties in children and adolescents with type 1 diabetes (T1D).
METHODS
In a randomized, two-period crossover trial, 12 children, 16 adolescents, and 15 adults (6-11, 12-17, and 18-64 years) received 0.2 U/kg double-blindsingle-dose subcutaneous faster aspart or IAsp followed by a standardized liquid meal test.
RESULTS
Across age groups, the pharmacokinetic profile was left-shifted including greater early exposure for faster aspart vs IAsp irrespective of free or total IAsp assay. Onset of appearance occurred 2.4 to 5.0 minutes (free) or 1.8 to 3.0 minutes (total) earlier for faster aspart vs IAsp (P < .05). Treatment ratios (faster aspart/IAsp) for 0 to 30 minutes IAsp exposure were 1.60 to 2.11 and 1.62 to 1.96, respectively (children, free: P = .062; otherwise P < .05). The ratio of free/total IAsp for overall exposure (AUC
CONCLUSIONS
In children and adolescents with T1D, faster aspart provides ultrafast pharmacokinetics irrespective of free or total IAsp assay. Elevated anti-IAsp antibodies are associated with higher total IAsp concentration, but do not impact faster aspart and IAsp glucose-lowering effect.
Identifiants
pubmed: 32306477
doi: 10.1111/pedi.13026
pmc: PMC7383777
doi:
Substances chimiques
Blood Glucose
0
Insulin Antibodies
0
Insulin Aspart
D933668QVX
Types de publication
Journal Article
Randomized Controlled Trial
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
781-790Informations de copyright
© 2020 The Authors. Pediatric Diabetes published by John Wiley & Sons Ltd.
Références
Pediatr Diabetes. 2016 Dec;17(8):642-649
pubmed: 26782928
Diabetes Care. 2005 Sep;28(9):2100-5
pubmed: 16123473
Pediatr Diabetes. 2011 Mar;12(2):78-84
pubmed: 20522172
Diabetes Care. 2005 Sep;28(9):2161-9
pubmed: 16123484
Best Pract Res Clin Endocrinol Metab. 2013 Oct;27(5):631-45
pubmed: 24094635
Lancet. 1977 Jul 9;2(8028):56-8
pubmed: 69146
Pediatr Diabetes. 2020 Aug;21(5):781-790
pubmed: 32306477
Diabetes Care. 2017 Jul;40(7):951-957
pubmed: 28483786
Eur J Endocrinol. 2005 Dec;153(6):907-13
pubmed: 16322398
Diabetes Obes Metab. 2018 Dec;20(12):2885-2893
pubmed: 30259644
J Diabetes Sci Technol. 2012 Jul 01;6(4):797-801
pubmed: 22920804
Diabetes Obes Metab. 2018 May;20(5):1148-1155
pubmed: 29316130
Curr Diab Rep. 2017 Sep 23;17(11):101
pubmed: 28940145
Diabetes Care. 2002 May;25(5):876-82
pubmed: 11978684
Clin Pharmacokinet. 2019 May;58(5):639-649
pubmed: 30402720
Pediatr Diabetes. 2011 Mar;12(2):75-7
pubmed: 21352424
Diabetes Res. 1988 Feb;7(2):65-9
pubmed: 3293878
Clin Pharmacokinet. 2017 May;56(5):551-559
pubmed: 28205039
Diabetes Care. 1989 Oct;12(9):641-8
pubmed: 2676431
Endocr Rev. 2007 Oct;28(6):625-52
pubmed: 17785428
Diabetes Care. 2013 May;36(5):1384-95
pubmed: 23589542
Pharm Res. 2019 Feb 11;36(3):49
pubmed: 30746556
Clin Lab. 2003;49(3-4):113-21
pubmed: 12705692
Diabetes Care. 2010 May;33(5):1009-12
pubmed: 20150302
Diabetologia. 1985 Jun;28(6):330-4
pubmed: 3899818
Clin Chem. 1987 Jan;33(1):93-6
pubmed: 3542298
Diabetologia. 2015 Apr;58(4):687-90
pubmed: 25537835
Pediatr Diabetes. 2014 Sep;15 Suppl 20:180-92
pubmed: 25040141
Eur J Clin Chem Clin Biochem. 1997 May;35(5):365-7
pubmed: 9189740
Pediatr Diabetes. 2017 Dec;18(8):903-910
pubmed: 28165180
Diabetes Care. 2019 Jul;42(7):1255-1262
pubmed: 31076415
Metabolism. 1986 Jul;35(7):649-56
pubmed: 3523119