Prospective observational study on the pharmacokinetic properties of the Irrua ribavirin regimen used in routine clinical practice in patients with Lassa fever in Nigeria.
clinical pharmacology
infectious diseases
virology
Journal
BMJ open
ISSN: 2044-6055
Titre abrégé: BMJ Open
Pays: England
ID NLM: 101552874
Informations de publication
Date de publication:
16 04 2020
16 04 2020
Historique:
entrez:
19
4
2020
pubmed:
19
4
2020
medline:
21
4
2021
Statut:
epublish
Résumé
Lassa fever (LF) is a severe and often fatal systemic disease in humans and affects a large number of countries in West Africa. Treatment options are limited to supportive care and the broad-spectrum antiviral agent ribavirin. However, evidence for ribavirin efficacy in patients with LF is poor and pharmacokinetic (PK) data are not available.Irrua Specialist Teaching Hospital (ISTH) developed an intravenous ribavirin regimen different to the WHO recommendation. Apart from a lower total daily dose the drug is usually administered once per day which reduces the exposure of personnel to patients with LF. The aim of this study is to characterise the PK of the Irrua ribavirin regimen. This prospective, observational clinical study will assess PK properties of the Irrua ribavirin regimen on routinely ribavirin-treated patients with LF at ISTH, a referral hospital serving 19 local governmental areas in a LF endemic zone in Nigeria. Participants will be adults with PCR-confirmed LF. The primary objective is to describe classical PK parameters for ribavirin (maximum plasma drug concentration, time to maximum plasma drug concentration, area under the plasma drug concentration vs time curve, half-life time T1/2, volume of distribution). Blood samples will be collected at 0.5, 1, 3, 5, 8, 12 and 24 hours after doses on day 1, day 4 and day 10 of ribavirin treatment. Ribavirin plasma concentrations will be determined using liquid chromatography coupled to tandem mass spectrometry. The study will be conducted in compliance with the protocol, the Declaration of Helsinki, Good Clinical Practice (GCP) and the Nigerian National Code for Health Research Ethics. The protocol has received approval by the Health Research Ethics Committee of ISTH. Results will be made available to LF survivors, their caregivers, the funders, LF research society and other researchers. ISRCTN11104750.
Identifiants
pubmed: 32303517
pii: bmjopen-2020-036936
doi: 10.1136/bmjopen-2020-036936
pmc: PMC7200043
doi:
Substances chimiques
Ribavirin
49717AWG6K
Banques de données
ISRCTN
['ISRCTN11104750']
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e036936Informations de copyright
© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.
Déclaration de conflit d'intérêts
Competing interests: None declared.
Références
Vopr Virusol. 1990 Mar-Apr;35(2):151-2
pubmed: 2389569
Vector Borne Zoonotic Dis. 2001 Winter;1(4):269-81
pubmed: 12653127
J Infect Dis. 1980 May;141(5):580-9
pubmed: 6768812
Antimicrob Agents Chemother. 1999 Oct;43(10):2451-6
pubmed: 10508023
Rev Infect Dis. 1989 May-Jun;11 Suppl 4:S783-9
pubmed: 2749109
J Clin Microbiol. 2010 Jun;48(6):2009-13
pubmed: 20351210
J Infect Dis. 1984 Mar;149(3):420-7
pubmed: 6715898
J Infect Dis. 1987 Mar;155(3):456-64
pubmed: 3805773
Am J Trop Med Hyg. 1986 Mar;35(2):401-7
pubmed: 3953952
BMJ. 1995 Sep 30;311(7009):857-9
pubmed: 7580496
Science. 1974 Jul 19;185(4147):263-5
pubmed: 4833828
J Clin Microbiol. 2011 Mar;49(3):1157-61
pubmed: 21191050
Lancet. 1979 Feb 3;1(8110):268-9
pubmed: 84919
J Infect Dis. 2016 Mar 15;213(6):934-8
pubmed: 26531247
J Infect Dis. 1987 Mar;155(3):445-55
pubmed: 3805772
Lancet. 2018 Feb 24;391(10122):728
pubmed: 29486937
N Engl J Med. 1986 Jan 2;314(1):20-6
pubmed: 3940312
PLoS Negl Trop Dis. 2017 Feb 23;11(2):e0005389
pubmed: 28231247
J Trop Med Hyg. 1992 Jun;95(3):197-201
pubmed: 1597876
CPT Pharmacometrics Syst Pharmacol. 2015 Jan;4(1):e00008
pubmed: 26225222
Semin Liver Dis. 1999;19 Suppl 1:17-24
pubmed: 10349689
Int J Infect Dis. 2019 Oct;87:15-20
pubmed: 31357056
J Chromatogr B Analyt Technol Biomed Life Sci. 2007 Sep 1;856(1-2):358-64
pubmed: 17574937
Nat Med. 2000 Dec;6(12):1375-9
pubmed: 11100123
CPT Pharmacometrics Syst Pharmacol. 2017 Aug;6(8):512-522
pubmed: 28378945
PLoS Negl Trop Dis. 2012;6(9):e1839
pubmed: 23029594
Proc Natl Acad Sci U S A. 2001 Jun 5;98(12):6895-900
pubmed: 11371613
AAPS J. 2012 Sep;14(3):571-80
pubmed: 22639111
Am J Trop Med Hyg. 1970 Jul;19(4):670-6
pubmed: 4246571