Evaluation of Hydroxychloroquine Blood Concentrations and Effects in Childhood-Onset Systemic Lupus Erythematosus.
hydroxychloroquine
pharmacodynamics
pharmacokinetics
systemic lupus erythematosus
Journal
Pharmaceuticals (Basel, Switzerland)
ISSN: 1424-8247
Titre abrégé: Pharmaceuticals (Basel)
Pays: Switzerland
ID NLM: 101238453
Informations de publication
Date de publication:
17 Mar 2021
17 Mar 2021
Historique:
received:
15
02
2021
revised:
08
03
2021
accepted:
12
03
2021
entrez:
3
4
2021
pubmed:
4
4
2021
medline:
4
4
2021
Statut:
epublish
Résumé
Hydroxychloroquine (HCQ) is an antimalarial agent given to patients with systemic lupus erythematosus (SLE) as first-line therapy. It alleviates childhood-onset systemic lupus erythematosus cSLE skin and musculoskeletal disease, decreasing disease activity and flares. HCQ concentration-effect relationships in children remains unknown. This study aimed to investigate the pharmacokinetics of HCQ and possible concentration-effect relationships. HCQ blood concentrations and effects were obtained during clinical follow-up on different occasions. cSLE flares were defined using the SLE Disease Activity Index (SLEDAI); flare was denoted by a SLEDAI score > 6. Blood concentration was measured using high-performance liquid chromatography with fluorometric detection. Statistical analysis was performed using a nonlinear mixed-effect approach with the Monolix software. A total of 168 blood samples were obtained from 55 pediatric patients. HCQ apparent blood clearance (CL/F) was dependent on patients' bodyweight and platelet count. Patients with active cSLE had a lower mean blood HCQ concentration compared with inactive cSLE patients (536 ± 294 vs. 758 ± 490 ng/mL, We developed the first HCQ blood concentration-effect relationship for cSLE associated with active or non-active disease status. A prospective randomized study is necessary to confirm these results.
Sections du résumé
BACKGROUND
BACKGROUND
Hydroxychloroquine (HCQ) is an antimalarial agent given to patients with systemic lupus erythematosus (SLE) as first-line therapy. It alleviates childhood-onset systemic lupus erythematosus cSLE skin and musculoskeletal disease, decreasing disease activity and flares. HCQ concentration-effect relationships in children remains unknown. This study aimed to investigate the pharmacokinetics of HCQ and possible concentration-effect relationships.
METHODS
METHODS
HCQ blood concentrations and effects were obtained during clinical follow-up on different occasions. cSLE flares were defined using the SLE Disease Activity Index (SLEDAI); flare was denoted by a SLEDAI score > 6. Blood concentration was measured using high-performance liquid chromatography with fluorometric detection. Statistical analysis was performed using a nonlinear mixed-effect approach with the Monolix software.
RESULTS
RESULTS
A total of 168 blood samples were obtained from 55 pediatric patients. HCQ apparent blood clearance (CL/F) was dependent on patients' bodyweight and platelet count. Patients with active cSLE had a lower mean blood HCQ concentration compared with inactive cSLE patients (536 ± 294 vs. 758 ± 490 ng/mL,
CONCLUSION
CONCLUSIONS
We developed the first HCQ blood concentration-effect relationship for cSLE associated with active or non-active disease status. A prospective randomized study is necessary to confirm these results.
Identifiants
pubmed: 33802811
pii: ph14030273
doi: 10.3390/ph14030273
pmc: PMC8002378
pii:
doi:
Types de publication
Journal Article
Langues
eng
Références
Ther Drug Monit. 2019 Aug;41(4):476-482
pubmed: 30807538
Intern Med J. 2013 May;43(5):547-53
pubmed: 23425382
J Am Acad Dermatol. 2016 Apr;74(4):693-9.e3
pubmed: 26850655
Annu Rev Pharmacol Toxicol. 2008;48:303-32
pubmed: 17914927
Arthritis Rheum. 2008 Feb;58(2):556-62
pubmed: 18240232
Clin Cancer Res. 2014 Feb 1;20(3):754-63
pubmed: 24218510
Ann Rheum Dis. 2019 Jun;78(6):736-745
pubmed: 30926722
Ann Rheum Dis. 2014 Jun;73(6):958-67
pubmed: 24739325
J Rheumatol. 2000 Jul;27(7):1656-60
pubmed: 10914847
Therapie. 2021 Jan 28;:
pubmed: 33558079
J Clin Rheumatol. 2008 Aug;14(4):195-201
pubmed: 18636020
Lupus. 2000;9(8):601-6
pubmed: 11035435
Arthritis Rheum. 2006 Oct;54(10):3284-90
pubmed: 17009263
Ther Drug Monit. 2016 Apr;38(2):259-67
pubmed: 26587870
Arthritis Care Res (Hoboken). 2020 Jan 31;:
pubmed: 32004406
N Engl J Med. 1991 Jan 17;324(3):150-4
pubmed: 1984192
Arthritis Rheum. 2002 Jun;46(6):1460-9
pubmed: 12115175
Br J Clin Pharmacol. 1988 Sep;26(3):303-13
pubmed: 3179169
Arthritis Rheum. 2009 Jan 15;61(1):13-20
pubmed: 19116979
Curr Drug Metab. 2011 Feb;12(2):154-72
pubmed: 21395541
Lupus. 2011 Oct;20(11):1187-92
pubmed: 21768176
Arthritis Rheumatol. 2015 May;67(8):2176-84
pubmed: 25989906
Ann Rheum Dis. 2017 Nov;76(11):1788-1796
pubmed: 28630236