Ribavarin for treating Lassa fever: A systematic review of pre-clinical studies and implications for human dosing
Issued Date
2022-03-01
Resource Type
ISSN
19352727
eISSN
19352735
Scopus ID
2-s2.0-85127662117
Pubmed ID
35353804
Journal Title
PLoS Neglected Tropical Diseases
Volume
16
Issue
3
Rights Holder(s)
SCOPUS
Bibliographic Citation
PLoS Neglected Tropical Diseases Vol.16 No.3 (2022)
Suggested Citation
Salam A.P. Ribavarin for treating Lassa fever: A systematic review of pre-clinical studies and implications for human dosing. PLoS Neglected Tropical Diseases Vol.16 No.3 (2022). doi:10.1371/journal.pntd.0010289 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/86046
Title
Ribavarin for treating Lassa fever: A systematic review of pre-clinical studies and implications for human dosing
Author(s)
Author's Affiliation
Faculty of Tropical Medicine, Mahidol University
Université de Bordeaux
The Wellcome Centre for Human Genetics
Centre Hospitalier Universitaire de Treichville
Centre Hospitalier Universitaire de Bordeaux
Nuffield Department of Medicine
Alliance for International Medical Action
UK Public Health Rapid Support Team
Université de Bordeaux
The Wellcome Centre for Human Genetics
Centre Hospitalier Universitaire de Treichville
Centre Hospitalier Universitaire de Bordeaux
Nuffield Department of Medicine
Alliance for International Medical Action
UK Public Health Rapid Support Team
Other Contributor(s)
Abstract
Ribavirin is currently the standard of care for treating Lassa fever. However, the human clinical trial data supporting its use suffer from several serious flaws that render the results and conclusions unreliable. We performed a systematic review of available pre-clinical data and human pharmacokinetic data on ribavirin in Lassa. In in-vitro studies, the EC50 of ribavirin ranged from 0.6 μg/ml to 21.72 μg/ml and the EC90 ranged from 1.5 μg/ml to 29 μg/ml. The mean EC50 was 7 μg/ml and the mean EC90 was 15 μg/ml. Human PK data in patients with Lassa fever was sparse and did not allow for estimation of concentration profiles or pharma-cokinetic parameters. Pharmacokinetic modelling based on healthy human data suggests that the concentration profiles of current ribavirin regimes only exceed the mean EC50 for less than 20% of the time and the mean EC90 for less than 10% of the time, raising the pos-sibility that the current ribavirin regimens in clinical use are unlikely to reliably achieve serum concentrations required to inhibit Lassa virus replication. The results of this review highlight serious issues with the evidence, which, by today standards, would be unlikely to support the transition of ribavirin from pre-clinical studies to human clinical trials. Additional pre-clini-cal studies are needed before embarking on expensive and challenging clinical trials of riba-virin in Lassa fever.
