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Population Pharmacokinetics of Orally Administered Clindamycin to Treat Prosthetic Joint Infections: A Prospective Study

A population PK model of clindamycin orally administered to patients with prosthetic joint infections (PJIs) was developed using NONMEM 7.5. Monte-Carlo simulations were run to determine the probability of obtaining bone clindamycin concentrations equal to at least the MIC or four times the MIC for...

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Autores principales: Mimram, Léo, Magréault, Sophie, Kerroumi, Younes, Salmon, Dominique, Kably, Benjamin, Marmor, Simon, Jannot, Anne-Sophie, Jullien, Vincent, Zeller, Valérie
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9686637/
https://www.ncbi.nlm.nih.gov/pubmed/36358117
http://dx.doi.org/10.3390/antibiotics11111462
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author Mimram, Léo
Magréault, Sophie
Kerroumi, Younes
Salmon, Dominique
Kably, Benjamin
Marmor, Simon
Jannot, Anne-Sophie
Jullien, Vincent
Zeller, Valérie
author_facet Mimram, Léo
Magréault, Sophie
Kerroumi, Younes
Salmon, Dominique
Kably, Benjamin
Marmor, Simon
Jannot, Anne-Sophie
Jullien, Vincent
Zeller, Valérie
author_sort Mimram, Léo
collection PubMed
description A population PK model of clindamycin orally administered to patients with prosthetic joint infections (PJIs) was developed using NONMEM 7.5. Monte-Carlo simulations were run to determine the probability of obtaining bone clindamycin concentrations equal to at least the MIC or four times the MIC for several MIC values and dosing regimens. One hundred and forty plasma concentrations prospectively obtained from 20 patients with PJIs were used. A one-compartment model with first-order absorption and elimination appropriately described the data. Mean PK-parameter estimates (F being the bioavailability) were: apparent clearance, CL/F = 23 L/h, apparent distribution volume, V/F = 103 l and absorption rate constant, Ka = 3.53/h, with respective interindividual variabilities (coefficients of variation) of 14.4%, 8.2% and 59.6%. Neither goodness-of-fit curves nor visual predictive checks indicated bias. The currently recommended 600 mg q8h regimen provided a high probability of obtaining concentrations equal to at least the MIC, except for MIC ≥ the clinical breakpoint for Staphylococcus spp. (0.25 mg/L). For such MIC values, higher daily doses and q6h regimens could be considered.
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spelling pubmed-96866372022-11-25 Population Pharmacokinetics of Orally Administered Clindamycin to Treat Prosthetic Joint Infections: A Prospective Study Mimram, Léo Magréault, Sophie Kerroumi, Younes Salmon, Dominique Kably, Benjamin Marmor, Simon Jannot, Anne-Sophie Jullien, Vincent Zeller, Valérie Antibiotics (Basel) Article A population PK model of clindamycin orally administered to patients with prosthetic joint infections (PJIs) was developed using NONMEM 7.5. Monte-Carlo simulations were run to determine the probability of obtaining bone clindamycin concentrations equal to at least the MIC or four times the MIC for several MIC values and dosing regimens. One hundred and forty plasma concentrations prospectively obtained from 20 patients with PJIs were used. A one-compartment model with first-order absorption and elimination appropriately described the data. Mean PK-parameter estimates (F being the bioavailability) were: apparent clearance, CL/F = 23 L/h, apparent distribution volume, V/F = 103 l and absorption rate constant, Ka = 3.53/h, with respective interindividual variabilities (coefficients of variation) of 14.4%, 8.2% and 59.6%. Neither goodness-of-fit curves nor visual predictive checks indicated bias. The currently recommended 600 mg q8h regimen provided a high probability of obtaining concentrations equal to at least the MIC, except for MIC ≥ the clinical breakpoint for Staphylococcus spp. (0.25 mg/L). For such MIC values, higher daily doses and q6h regimens could be considered. MDPI 2022-10-23 /pmc/articles/PMC9686637/ /pubmed/36358117 http://dx.doi.org/10.3390/antibiotics11111462 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Mimram, Léo
Magréault, Sophie
Kerroumi, Younes
Salmon, Dominique
Kably, Benjamin
Marmor, Simon
Jannot, Anne-Sophie
Jullien, Vincent
Zeller, Valérie
Population Pharmacokinetics of Orally Administered Clindamycin to Treat Prosthetic Joint Infections: A Prospective Study
title Population Pharmacokinetics of Orally Administered Clindamycin to Treat Prosthetic Joint Infections: A Prospective Study
title_full Population Pharmacokinetics of Orally Administered Clindamycin to Treat Prosthetic Joint Infections: A Prospective Study
title_fullStr Population Pharmacokinetics of Orally Administered Clindamycin to Treat Prosthetic Joint Infections: A Prospective Study
title_full_unstemmed Population Pharmacokinetics of Orally Administered Clindamycin to Treat Prosthetic Joint Infections: A Prospective Study
title_short Population Pharmacokinetics of Orally Administered Clindamycin to Treat Prosthetic Joint Infections: A Prospective Study
title_sort population pharmacokinetics of orally administered clindamycin to treat prosthetic joint infections: a prospective study
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9686637/
https://www.ncbi.nlm.nih.gov/pubmed/36358117
http://dx.doi.org/10.3390/antibiotics11111462
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