Population pharmacokinetic analysis of lopinavir in HIV negative individuals exposed to SARS-CoV-2: a COPEP (COronavirus Post-Exposure Prophylaxis) sub-study.
COVID
Lopinavir
NONMEM
Pharmacometrics
Therapeutic drug monitoring
Journal
BMC pharmacology & toxicology
ISSN: 2050-6511
Titre abrégé: BMC Pharmacol Toxicol
Pays: England
ID NLM: 101590449
Informations de publication
Date de publication:
27 09 2023
27 09 2023
Historique:
received:
24
03
2023
accepted:
15
09
2023
medline:
4
10
2023
pubmed:
28
9
2023
entrez:
27
9
2023
Statut:
epublish
Résumé
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. 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 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 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.
Sections du résumé
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
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
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.
Identifiants
pubmed: 37759315
doi: 10.1186/s40360-023-00687-6
pii: 10.1186/s40360-023-00687-6
pmc: PMC10536696
doi:
Substances chimiques
Lopinavir
2494G1JF75
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
47Informations de copyright
© 2023. BioMed Central Ltd., part of Springer Nature.
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