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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...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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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. |
format | Online Article Text |
id | pubmed-9686637 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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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