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Population pharmacokinetic analysis of lopinavir in HIV negative individuals exposed to SARS-CoV-2: a COPEP (COronavirus Post-Exposure Prophylaxis) sub-study
BACKGROUND: Lopinavir/ritonavir (LPV/r) is a drug traditionally used for the treatment of HIV that has been repurposed as a potential post-exposure prophylaxis agent against COVID-19 in the COronavirus Post-Exposure Prophylaxis (COPEP) study. The present analysis aims to evaluate LPV levels in indiv...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10536696/ https://www.ncbi.nlm.nih.gov/pubmed/37759315 http://dx.doi.org/10.1186/s40360-023-00687-6 |
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author | Thoueille, Paul Delfraysse, Margot Andre, Pascal Buclin, Thierry Decosterd, Laurent A. Fedeli, Chiara Ustero, Pilar Calmy, Alexandra Guidi, Monia |
author_facet | Thoueille, Paul Delfraysse, Margot Andre, Pascal Buclin, Thierry Decosterd, Laurent A. Fedeli, Chiara Ustero, Pilar Calmy, Alexandra Guidi, Monia |
author_sort | Thoueille, Paul |
collection | PubMed |
description | BACKGROUND: Lopinavir/ritonavir (LPV/r) is a drug traditionally used for the treatment of HIV that has been repurposed as a potential post-exposure prophylaxis agent against COVID-19 in the COronavirus Post-Exposure Prophylaxis (COPEP) study. The present analysis aims to evaluate LPV levels in individuals exposed to SARS-CoV-2 versus people living with HIV (PLWH) by developing a population pharmacokinetic (popPK) model, while characterizing external and patient-related factors that might affect LPV exposure along with dose–response association. METHODS: We built a popPK model on 105 LPV concentrations measured in 105 HIV-negative COPEP individuals exposed to SARS-CoV-2, complemented with 170 LPV concentrations from 119 PLWH followed in our routine therapeutic drug-monitoring programme. Published LPV popPK models developed in PLWH and in COVID-19 patients were retrieved and validated in our study population by mean prediction error (MPE) and root mean square error (RMSE). The association between LPV model-predicted residual concentrations (C(min)) and the appearance of the COVID-19 infection in the COPEP participants was investigated. RESULTS: A one-compartment model with linear absorption and elimination best described LPV concentrations in both our analysis and in the majority of the identified studies. Globally, similar PK parameters were found in all PK models, and provided close MPEs (from -19.4% to 8.0%, with a RMSE of 3.4% to 49.5%). No statistically significant association between C(min) and the occurrence of a COVID-19 infection could be detected. CONCLUSION: Our analysis indicated that LPV circulating concentrations were similar between COPEP participants and PLWH, and that published popPK models described our data in a comparable way. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s40360-023-00687-6. |
format | Online Article Text |
id | pubmed-10536696 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-105366962023-09-29 Population pharmacokinetic analysis of lopinavir in HIV negative individuals exposed to SARS-CoV-2: a COPEP (COronavirus Post-Exposure Prophylaxis) sub-study Thoueille, Paul Delfraysse, Margot Andre, Pascal Buclin, Thierry Decosterd, Laurent A. Fedeli, Chiara Ustero, Pilar Calmy, Alexandra Guidi, Monia BMC Pharmacol Toxicol Research BACKGROUND: Lopinavir/ritonavir (LPV/r) is a drug traditionally used for the treatment of HIV that has been repurposed as a potential post-exposure prophylaxis agent against COVID-19 in the COronavirus Post-Exposure Prophylaxis (COPEP) study. The present analysis aims to evaluate LPV levels in individuals exposed to SARS-CoV-2 versus people living with HIV (PLWH) by developing a population pharmacokinetic (popPK) model, while characterizing external and patient-related factors that might affect LPV exposure along with dose–response association. METHODS: We built a popPK model on 105 LPV concentrations measured in 105 HIV-negative COPEP individuals exposed to SARS-CoV-2, complemented with 170 LPV concentrations from 119 PLWH followed in our routine therapeutic drug-monitoring programme. Published LPV popPK models developed in PLWH and in COVID-19 patients were retrieved and validated in our study population by mean prediction error (MPE) and root mean square error (RMSE). The association between LPV model-predicted residual concentrations (C(min)) and the appearance of the COVID-19 infection in the COPEP participants was investigated. RESULTS: A one-compartment model with linear absorption and elimination best described LPV concentrations in both our analysis and in the majority of the identified studies. Globally, similar PK parameters were found in all PK models, and provided close MPEs (from -19.4% to 8.0%, with a RMSE of 3.4% to 49.5%). No statistically significant association between C(min) and the occurrence of a COVID-19 infection could be detected. CONCLUSION: Our analysis indicated that LPV circulating concentrations were similar between COPEP participants and PLWH, and that published popPK models described our data in a comparable way. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s40360-023-00687-6. BioMed Central 2023-09-27 /pmc/articles/PMC10536696/ /pubmed/37759315 http://dx.doi.org/10.1186/s40360-023-00687-6 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
spellingShingle | Research Thoueille, Paul Delfraysse, Margot Andre, Pascal Buclin, Thierry Decosterd, Laurent A. Fedeli, Chiara Ustero, Pilar Calmy, Alexandra Guidi, Monia Population pharmacokinetic analysis of lopinavir in HIV negative individuals exposed to SARS-CoV-2: a COPEP (COronavirus Post-Exposure Prophylaxis) sub-study |
title | Population pharmacokinetic analysis of lopinavir in HIV negative individuals exposed to SARS-CoV-2: a COPEP (COronavirus Post-Exposure Prophylaxis) sub-study |
title_full | Population pharmacokinetic analysis of lopinavir in HIV negative individuals exposed to SARS-CoV-2: a COPEP (COronavirus Post-Exposure Prophylaxis) sub-study |
title_fullStr | Population pharmacokinetic analysis of lopinavir in HIV negative individuals exposed to SARS-CoV-2: a COPEP (COronavirus Post-Exposure Prophylaxis) sub-study |
title_full_unstemmed | Population pharmacokinetic analysis of lopinavir in HIV negative individuals exposed to SARS-CoV-2: a COPEP (COronavirus Post-Exposure Prophylaxis) sub-study |
title_short | Population pharmacokinetic analysis of lopinavir in HIV negative individuals exposed to SARS-CoV-2: a COPEP (COronavirus Post-Exposure Prophylaxis) sub-study |
title_sort | population pharmacokinetic analysis of lopinavir in hiv negative individuals exposed to sars-cov-2: a copep (coronavirus post-exposure prophylaxis) sub-study |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10536696/ https://www.ncbi.nlm.nih.gov/pubmed/37759315 http://dx.doi.org/10.1186/s40360-023-00687-6 |
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