Systemic Exposure to Hydroxychloroquine and its relationship with outcome in severely ill COVID-19 patients in New York City
Lyashchenko et al.,
Systemic Exposure to Hydroxychloroquine and its relationship with outcome in severely ill COVID-19 patients in..,
British Journal of Clinical Pharmacology, doi:10.1111/bcp.15489
Retrospective very late stage hospitalized patients in New York during the first wave, showing no significant relationship between HCQ levels and outcomes. Authors note that the patients with data were the sickest patients.
This study is excluded in the after exclusion results of meta
analysis:
substantial unadjusted
confounding by indication likely.
risk of death, 47.7% higher, RR 1.48, p < 0.001, treatment 389 of 1,419 (27.4%), control 341 of 1,837 (18.6%).
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Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates
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Lyashchenko et al., 12 Aug 2022, retrospective, USA, peer-reviewed, 6 authors, study period March 2020 - June 2020, average treatment delay 9.5 days.
Contact:
mty@cumc.columbia.edu, sc2752@cumc.columbia.edu.
Abstract: Lyashchenko Alex K (Orcid ID: 0000-0003-0629-0494)
Cremers Serge (Orcid ID: 0000-0002-6800-5532)
Systemic Exposure to Hydroxychloroquine and its relationship with outcome in severely ill
COVID-19 patients in New York City
Alex K Lyashchenko1, Yifan Yu2, Donald J McMahon3, Robert Bies2, Michael T Yin3, Serge
Cremers2,3
1
Department of Pathology and Cell Biology, Vagelos College of Physicians and Surgeons,
Columbia University Irving Medical Center, New York, NY, United States of America
2
Department of Pharmaceutical Sciences, University at Buffalo, Buffalo, NY, United States of
America
3
Department of Medicine, Vagelos College of Physicians and Surgeons, Columbia University
Irving Medical Center, New York, NY, United States of America
Corresponding authors:
Michael T Yin, MD
Associate Professor of Medicine
Division of Infectious Diseases
Department of Medicine
Columbia University Irving Medical Center
Email: mty@cumc.columbia.edu
Serge Cremers, PharmD, PhD
Professor of Pathology and Cell Biology and Medicine
Division of Laboratory Medicine
Department of Pathology and Cell Biology
Columbia University Irving Medical Center
This article has been accepted for publication and undergone full peer review but has not been
through the copyediting, typesetting, pagination and proofreading process which may lead to
differences between this version and the Version of Record. Please cite this article as doi:
10.1111/bcp.15489
This article is protected by copyright. All rights reserved.
Email: sc2752@cumc.columbia.edu
Running head: PK/PD of Hydroxychloroquine in NYC COVID-19-patients
Keywords: COVID-19, Hydroxychloroquine, Pharmacokinetics, Clinical outcome, PK/PD
Abstract
Aim: To investigate the relationship between systemic exposure to Hydroxychloroquine
(HCQ) and its metabolite Desethylhydroxychloroquine (DHCQ) and clinical outcome in
severely ill patients treated with a standard oral dose regimen of HCQ during the first wave
of COVID-19 in New York City.
Methods: We correlated retrospective clinical data with drug exposure prospectively
assessed from convenience samples using population pharmacokinetics and Bayesian
estimation. Systemic exposure was assessed in 215 patients admitted to ICU or COVID-ward
for whom an interleukin-6 level was requested and who were still alive 24h after the last
dose of HCQ. Patients received oral HCQ 600 mg bid on day 1 followed by 4 days of 400 mg
qd.
Results: Fifty-three% of the patients were intubated at 5.4 ± 6.4 days after admission. 26.5%
died at an average of 32.2 ± 19.1 days. QTc at admission was 448 ± 34 msec. Systemic
exposure to HCQ and DHCQ demonstrated substantial variability. Cumulative HCQ AUC 0-inf
=71.4 ± 19.3 h*mg/L and DHCQ AUC0-inf= 56.5 ± 28.3 h*mg/L. Variability in systemic
exposure was not clearly explained by renal function, liver function or inflammatory state. In
turn, systemic exposure did not correlate with intubation status, survival or QTc
prolongation.
Conclusion: This study in severely ill patients was not able to find any relationship between
systemic exposure to HCQ and DHCQ and clinical outcome at a routine dose regimen and
adds to the growing body of evidence that oral HCQ does not alter the course of disease in
COVID-19 patients.
This article is protected by copyright. All rights reserved.
What is already known about this subject
-
Hydroxychloroquine (HCQ) has been used for the treatment of patients with COVID19 infections, especially during the early phase of the..
Late treatment
is less effective
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