Ribavarin for treating Lassa fever: a systematic review of pre-clinical studies and implications for human dosing
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 pharmacokine...
| Main Authors: | , , , , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
Public Library of Science
2022
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| _version_ | 1797106642085478400 |
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| author | Salam, AP Duvignaud, A Jaspard, M Malvy, D Carroll, M Tarning, J Olliaro, PL Horby, PW |
| author_facet | Salam, AP Duvignaud, A Jaspard, M Malvy, D Carroll, M Tarning, J Olliaro, PL Horby, PW |
| author_sort | Salam, AP |
| collection | OXFORD |
| description | 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 pharmacokinetic 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 possibility 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-clinical studies are needed before embarking on expensive and challenging clinical trials of ribavirin in Lassa fever. |
| first_indexed | 2024-03-07T07:03:55Z |
| format | Journal article |
| id | oxford-uuid:e514cdfd-9afb-47fa-a9d9-db6811091ab3 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T07:03:55Z |
| publishDate | 2022 |
| publisher | Public Library of Science |
| record_format | dspace |
| spelling | oxford-uuid:e514cdfd-9afb-47fa-a9d9-db6811091ab32022-04-14T13:33:13ZRibavarin for treating Lassa fever: a systematic review of pre-clinical studies and implications for human dosingJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:e514cdfd-9afb-47fa-a9d9-db6811091ab3EnglishSymplectic ElementsPublic Library of Science2022Salam, APDuvignaud, AJaspard, MMalvy, DCarroll, MTarning, JOlliaro, PLHorby, PWRibavirin 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 pharmacokinetic 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 possibility 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-clinical studies are needed before embarking on expensive and challenging clinical trials of ribavirin in Lassa fever. |
| spellingShingle | Salam, AP Duvignaud, A Jaspard, M Malvy, D Carroll, M Tarning, J Olliaro, PL Horby, PW Ribavarin for treating Lassa fever: a systematic review of pre-clinical studies and implications for human dosing |
| title | Ribavarin for treating Lassa fever: a systematic review of pre-clinical studies and implications for human dosing |
| title_full | Ribavarin for treating Lassa fever: a systematic review of pre-clinical studies and implications for human dosing |
| title_fullStr | Ribavarin for treating Lassa fever: a systematic review of pre-clinical studies and implications for human dosing |
| title_full_unstemmed | Ribavarin for treating Lassa fever: a systematic review of pre-clinical studies and implications for human dosing |
| title_short | Ribavarin for treating Lassa fever: a systematic review of pre-clinical studies and implications for human dosing |
| title_sort | ribavarin for treating lassa fever a systematic review of pre clinical studies and implications for human dosing |
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