학술논문
Pharmacokinetics and Safety of Remdesivir in Pregnant and Non-Pregnant Women with COVID-19: Results from IMPAACT 2032.
Document Type
Academic Journal
Author
Brooks KM; Department of Pharmaceutical Sciences, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.; Baltrusaitis K; Center for Biostatistics in AIDS Research (CBAR), Harvard T.H. Chan School of Public Health, Boston, MA, USA.; Clarke DF; Section of Pediatric Infectious Diseases, Boston Medical Center, Boston, MA, USA.; Nachman S; Division of Pediatric Infectious Diseases, Stony Brook Children's Hospital, Stony Brook, NY, USA.; Jao J; Division of Pediatric Infectious Diseases, Division of Adult Infectious Diseases, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.; Purswani MU; Division of Pediatric Infectious Diseases, BronxCare Health System (Affiliated with Icahn School of Medicine at Mount Sinai), Bronx, NY, USA.; Agwu A; Department of Pediatric Infectious Disease, Johns Hopkins University School of Medicine, Baltimore, MD, United States.; Beneri C; Division of Pediatric Infectious Diseases, Stony Brook Children's Hospital, Stony Brook, NY, USA.; Deville JG; David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA.; Powis KM; Departments of Medicine and Pediatrics, Massachusetts General Hospital, Boston, MA, US.; Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, MA, US.; Stek AM; Division of Maternal Fetal Medicine, Department of Obstetrics and Gynecology, Keck School of Medicine University of Southern California, Los Angeles, CA, USA.; Eke AC; Division of Maternal Fetal Medicine, Department of Gynecology & Obstetrics, Johns Hopkins University School of Medicine, Baltimore, MD, USA.; Division of Clinical Pharmacology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.; Shapiro DE; Center for Biostatistics in AIDS Research (CBAR), Harvard T.H. Chan School of Public Health, Boston, MA, USA.; Capparelli E; Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, La Jolla, CA.; Pediatrics Department, School of Medicine-Rady Children's Hospital San Diego, University of California San Diego, San Diego, CA.; Greene E; FHI 360, IMPAACT Operations Center, Durham NC, US.; George K; FHI 360, IMPAACT Operations Center, Durham NC, US.; Yin DE; Division of AIDS, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD, USA.; Jean-Philippe P; Division of AIDS, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD, USA.; Chakhtoura N; National Institute of Child Health and Human Development, Bethesda, MD, USA.; Bone F; Frontier Science & Technology Research Foundation (FSTRF), Inc., Amherst, NY, USA.; Bacon K; Frontier Science & Technology Research Foundation (FSTRF), Inc., Amherst, NY, USA.; Johnston B; Frontier Science & Technology Research Foundation (FSTRF), Inc., Amherst, NY, USA.; Reding C; Frontier Science & Technology Research Foundation (FSTRF), Inc., Amherst, NY, USA.; Kersey K; Gilead Sciences, Inc., Foster City, CA, USA.; Humeniuk R; Gilead Sciences, Inc., Foster City, CA, USA.; Best BM; Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, La Jolla, CA.; Pediatrics Department, School of Medicine-Rady Children's Hospital San Diego, University of California San Diego, San Diego, CA.; Mirochnick M; Boston University Chobanian and Avedisian School of Medicine, Boston, MA, USA.; Momper JD; Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, La Jolla, CA.
Source
Publisher: Oxford University Press Country of Publication: United States NLM ID: 0413675 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1537-6613 (Electronic) Linking ISSN: 00221899 NLM ISO Abbreviation: J Infect Dis Subsets: MEDLINE
Subject
Language
English
Abstract
Background: Pregnant people with COVID-19 experience higher risk for severe disease and adverse pregnancy outcomes, but no pharmacokinetic (PK) data exist to support dosing of COVID-19 therapeutics during pregnancy. We report PK and safety data for intravenous remdesivir in pregnancy.
Methods: IMPAACT 2032 was a phase IV prospective, open-label, non-randomized opportunistic study of hospitalized pregnant and non-pregnant women receiving intravenous remdesivir as part of clinical care. Intensive PK sampling was performed on infusion days 3, 4, or 5 with collection of plasma and peripheral blood mononuclear cells (PBMCs). Safety data were recorded from first infusion through 4 weeks post-last infusion and at delivery. Geometric mean ratios (GMR) (90% confidence intervals [CI]) of PK parameters between pregnant and non-pregnant women were calculated.
Results: Fifty-three participants initiated remdesivir (25 pregnant; median (IQR) gestational age 27.6 (24.9, 31.0) weeks). Plasma exposures of remdesivir, its two major metabolites (GS-704277 and GS-441524), and the free remdesivir fraction were similar between pregnant and non-pregnant participants. Concentrations of the active triphosphate (GS-443902) in PBMCs increased 2.04-fold (90% CI 1.35, 3.03) with each additional infusion in non-pregnant versus pregnant participants. Three adverse events in non-pregnant participants were related to treatment (one Grade 3; two Grade 2 resulting in treatment discontinuation). There were no treatment-related adverse pregnancy outcomes or congenital anomalies detected.
Conclusions: Plasma remdesivir PK parameters were comparable between pregnant and non-pregnant women, and no safety concerns were identified based on our limited data. These findings suggest no dose adjustments are indicated for intravenous remdesivir during pregnancy.
(© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)
Methods: IMPAACT 2032 was a phase IV prospective, open-label, non-randomized opportunistic study of hospitalized pregnant and non-pregnant women receiving intravenous remdesivir as part of clinical care. Intensive PK sampling was performed on infusion days 3, 4, or 5 with collection of plasma and peripheral blood mononuclear cells (PBMCs). Safety data were recorded from first infusion through 4 weeks post-last infusion and at delivery. Geometric mean ratios (GMR) (90% confidence intervals [CI]) of PK parameters between pregnant and non-pregnant women were calculated.
Results: Fifty-three participants initiated remdesivir (25 pregnant; median (IQR) gestational age 27.6 (24.9, 31.0) weeks). Plasma exposures of remdesivir, its two major metabolites (GS-704277 and GS-441524), and the free remdesivir fraction were similar between pregnant and non-pregnant participants. Concentrations of the active triphosphate (GS-443902) in PBMCs increased 2.04-fold (90% CI 1.35, 3.03) with each additional infusion in non-pregnant versus pregnant participants. Three adverse events in non-pregnant participants were related to treatment (one Grade 3; two Grade 2 resulting in treatment discontinuation). There were no treatment-related adverse pregnancy outcomes or congenital anomalies detected.
Conclusions: Plasma remdesivir PK parameters were comparable between pregnant and non-pregnant women, and no safety concerns were identified based on our limited data. These findings suggest no dose adjustments are indicated for intravenous remdesivir during pregnancy.
(© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)