Effect of Systemic Inflammatory Response to SARS-CoV-2 on Lopinavir and Hydroxychloroquine Plasma Concentrations.
Adult
Aged
Aged, 80 and over
Antibodies, Monoclonal, Humanized
/ therapeutic use
Antiviral Agents
/ blood
Betacoronavirus
/ drug effects
Biomarkers
/ blood
C-Reactive Protein
/ metabolism
COVID-19
Coronavirus Infections
/ drug therapy
Cytokine Release Syndrome
/ drug therapy
Drug Administration Schedule
Drug Combinations
Female
Hospitals, University
Humans
Hydroxychloroquine
/ blood
Length of Stay
/ statistics & numerical data
Lopinavir
/ blood
Male
Middle Aged
Pandemics
Pneumonia, Viral
/ drug therapy
Retrospective Studies
Ritonavir
/ blood
SARS-CoV-2
Severity of Illness Index
Survival Analysis
COVID-19
hydroxychloroquine
inflammation
levels
lopinavir-ritonavir
Journal
Antimicrobial agents and chemotherapy
ISSN: 1098-6596
Titre abrégé: Antimicrob Agents Chemother
Pays: United States
ID NLM: 0315061
Informations de publication
Date de publication:
20 08 2020
20 08 2020
Historique:
received:
09
06
2020
accepted:
06
07
2020
pubmed:
10
7
2020
medline:
4
9
2020
entrez:
10
7
2020
Statut:
epublish
Résumé
Coronavirus disease 2019 (COVID-19) leads to inflammatory cytokine release, which can downregulate the expression of metabolizing enzymes. This cascade affects drug concentrations in the plasma. We investigated the association between lopinavir (LPV) and hydroxychloroquine (HCQ) plasma concentrations and the levels of the acute-phase inflammation marker C-reactive protein (CRP). LPV plasma concentrations in 92 patients hospitalized at our institution were prospectively collected. Lopinavir-ritonavir was administered every 12 hours, 800/200 mg on day 1 and 400/100 mg on day 2 until day 5 or 7. HCQ was given at 800 mg, followed by 400 mg after 6, 24, and 48 h. Hematological, liver, kidney, and inflammation laboratory values were analyzed on the day of drug level determination. The median age of study participants was 59 (range, 24 to 85) years, and 71% were male. The median durations from symptom onset to hospitalization and treatment initiation were 7 days (interquartile range [IQR], 4 to 10) and 8 days (IQR, 5 to 10), respectively. The median LPV trough concentration on day 3 of treatment was 26.5 μg/ml (IQR, 18.9 to 31.5). LPV plasma concentrations positively correlated with CRP values (
Identifiants
pubmed: 32641296
pii: AAC.01177-20
doi: 10.1128/AAC.01177-20
pmc: PMC7449226
pii:
doi:
Substances chimiques
Antibodies, Monoclonal, Humanized
0
Antiviral Agents
0
Biomarkers
0
Drug Combinations
0
lopinavir-ritonavir drug combination
0
Lopinavir
2494G1JF75
Hydroxychloroquine
4QWG6N8QKH
C-Reactive Protein
9007-41-4
tocilizumab
I031V2H011
Ritonavir
O3J8G9O825
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
Copyright © 2020 American Society for Microbiology.
Références
AIDS. 2003 Jul 25;17(11):1710-1
pubmed: 12853760
Br J Clin Pharmacol. 2013 Sep;76(3):455-66
pubmed: 23305158
Infect Dis Ther. 2020 Sep;9(3):435-449
pubmed: 32462545
Clin Pharmacokinet. 2020 Mar;59(3):383-401
pubmed: 31583609
Clin Infect Dis. 2020 May 21;:
pubmed: 32435791
Clin Drug Investig. 2020 Jun;40(6):511-518
pubmed: 32337664
Br J Clin Pharmacol. 2018 Sep;84(9):1980-1988
pubmed: 29744898
JAMA. 2020 Apr 7;323(13):1239-1242
pubmed: 32091533
Psychopharmacology (Berl). 2016 May;233(9):1695-705
pubmed: 26032842
Antiviral Res. 2020 Jun;178:104786
pubmed: 32251767
N Engl J Med. 2020 May 7;382(19):1787-1799
pubmed: 32187464
J Clin Endocrinol Metab. 2000 Mar;85(3):1331-3
pubmed: 10720086
AIDS. 2008 May 11;22(8):931-5
pubmed: 18453852
Oncologist. 2018 Aug;23(8):943-947
pubmed: 29622697
J Clin Pharmacol. 2007 Aug;47(8):970-7
pubmed: 17615254
Eur J Clin Pharmacol. 2013 Oct;69(10):1795-800
pubmed: 23748748
J Biol Chem. 2005 Mar 11;280(10):9610-7
pubmed: 15632119
N Engl J Med. 2020 Aug 6;383(6):517-525
pubmed: 32492293
Mod Rheumatol. 2013 Sep;23(5):977-85
pubmed: 23099471
Drugs. 2010 Oct 1;70(14):1885-915
pubmed: 20836579
J Antimicrob Chemother. 2020 Sep 1;75(9):2704-2706
pubmed: 32407513
J Thromb Haemost. 2020 Jun;18(6):1320-1323
pubmed: 32329231
J Infect Dis. 2004 Jan 15;189(2):265-72
pubmed: 14722892
Expert Opin Drug Metab Toxicol. 2005 Dec;1(4):629-40
pubmed: 16863429
Ann Intern Med. 2020 May 12;:
pubmed: 32422065
Clin Pharmacol Ther. 2009 Apr;85(4):434-8
pubmed: 19212314
Drug Metab Dispos. 2011 Aug;39(8):1415-22
pubmed: 21555507
Open Forum Infect Dis. 2015 Jul 03;2(3):ofv098
pubmed: 26258155
Drug Metab Dispos. 2008 Feb;36(2):205-16
pubmed: 18218849
J Int AIDS Soc. 2020 Apr;23(4):e25489
pubmed: 32293807
J Antimicrob Chemother. 2020 Jun 17;:
pubmed: 32556272
Ther Drug Monit. 2016 Apr;38(2):259-67
pubmed: 26587870
J Antimicrob Chemother. 2020 Sep 1;75(9):2702-2704
pubmed: 32443151
Science. 2020 Apr 24;368(6489):409-412
pubmed: 32198291
Nat Commun. 2020 Jan 10;11(1):222
pubmed: 31924756
J Pharm Sci. 2016 Feb;105(2):884-890
pubmed: 26429523
N Engl J Med. 2020 Jun 18;382(25):2411-2418
pubmed: 32379955
Clin Infect Dis. 2020 May 11;:
pubmed: 32392332
Int J Antimicrob Agents. 2020 Aug;56(2):106028
pubmed: 32450198
J Acquir Immune Defic Syndr. 2015 Dec 15;70(5):510-4
pubmed: 26230332