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Population pharmacokinetic analysis and dosing regimen optimization of penicillin G in patients with infective endocarditis
BACKGROUND: This study was designed to evaluate the population pharmacokinetics (popPK) of penicillin G in patients with infective endocarditis and establish a dosage regimen based on pharmacokinetic data and clinical outcome. METHOD: Forty-six serum penicillin G samples from 25 individuals were ana...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4820900/ https://www.ncbi.nlm.nih.gov/pubmed/27051524 http://dx.doi.org/10.1186/s40780-016-0043-x |
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author | Komatsu, Toshiaki Inomata, Takayuki Watanabe, Ichiro Kobayashi, Masahiro Kokubun, Hideya Ako, Junya Atsuda, Koichiro |
author_facet | Komatsu, Toshiaki Inomata, Takayuki Watanabe, Ichiro Kobayashi, Masahiro Kokubun, Hideya Ako, Junya Atsuda, Koichiro |
author_sort | Komatsu, Toshiaki |
collection | PubMed |
description | BACKGROUND: This study was designed to evaluate the population pharmacokinetics (popPK) of penicillin G in patients with infective endocarditis and establish a dosage regimen based on pharmacokinetic data and clinical outcome. METHOD: Forty-six serum penicillin G samples from 25 individuals were analyzed using a nonlinear mixed-effects model. popPK were estimated using a one-compartment model. We created a receiver operating characteristic (ROC) curve for penicillin G efficacy and the ratio of its minimum concentration (Cmin)/minimum inhibitory concentration (MIC). Simulations were used to optimize the penicillin G dosage regimen using this ratio. RESULT: Estimated popPK were: CL (L/h) = 0.21 × creatinine clearance (CLcr) (mL/min), Vd (L) = 28.9. The areas under the ROC curves were 0.87 for clinical efficacy. The cut-off value of penicillin G Cmin/MIC was 60. The continuous administration of 1 million IU penicillin G/h was necessary to achieve a positive outcome for patients with normal renal function (CLcr ≥ 60 mL/min). CONCLUSION: Our findings suggest that population-based parameters are useful for evaluating penicillin G pharmacokinetics and that an individualized dosage should be determined based on a described dosage regimen. |
format | Online Article Text |
id | pubmed-4820900 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-48209002016-04-06 Population pharmacokinetic analysis and dosing regimen optimization of penicillin G in patients with infective endocarditis Komatsu, Toshiaki Inomata, Takayuki Watanabe, Ichiro Kobayashi, Masahiro Kokubun, Hideya Ako, Junya Atsuda, Koichiro J Pharm Health Care Sci Research Article BACKGROUND: This study was designed to evaluate the population pharmacokinetics (popPK) of penicillin G in patients with infective endocarditis and establish a dosage regimen based on pharmacokinetic data and clinical outcome. METHOD: Forty-six serum penicillin G samples from 25 individuals were analyzed using a nonlinear mixed-effects model. popPK were estimated using a one-compartment model. We created a receiver operating characteristic (ROC) curve for penicillin G efficacy and the ratio of its minimum concentration (Cmin)/minimum inhibitory concentration (MIC). Simulations were used to optimize the penicillin G dosage regimen using this ratio. RESULT: Estimated popPK were: CL (L/h) = 0.21 × creatinine clearance (CLcr) (mL/min), Vd (L) = 28.9. The areas under the ROC curves were 0.87 for clinical efficacy. The cut-off value of penicillin G Cmin/MIC was 60. The continuous administration of 1 million IU penicillin G/h was necessary to achieve a positive outcome for patients with normal renal function (CLcr ≥ 60 mL/min). CONCLUSION: Our findings suggest that population-based parameters are useful for evaluating penicillin G pharmacokinetics and that an individualized dosage should be determined based on a described dosage regimen. BioMed Central 2016-04-05 /pmc/articles/PMC4820900/ /pubmed/27051524 http://dx.doi.org/10.1186/s40780-016-0043-x Text en © Komatsu et al. 2016 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Research Article Komatsu, Toshiaki Inomata, Takayuki Watanabe, Ichiro Kobayashi, Masahiro Kokubun, Hideya Ako, Junya Atsuda, Koichiro Population pharmacokinetic analysis and dosing regimen optimization of penicillin G in patients with infective endocarditis |
title | Population pharmacokinetic analysis and dosing regimen optimization of penicillin G in patients with infective endocarditis |
title_full | Population pharmacokinetic analysis and dosing regimen optimization of penicillin G in patients with infective endocarditis |
title_fullStr | Population pharmacokinetic analysis and dosing regimen optimization of penicillin G in patients with infective endocarditis |
title_full_unstemmed | Population pharmacokinetic analysis and dosing regimen optimization of penicillin G in patients with infective endocarditis |
title_short | Population pharmacokinetic analysis and dosing regimen optimization of penicillin G in patients with infective endocarditis |
title_sort | population pharmacokinetic analysis and dosing regimen optimization of penicillin g in patients with infective endocarditis |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4820900/ https://www.ncbi.nlm.nih.gov/pubmed/27051524 http://dx.doi.org/10.1186/s40780-016-0043-x |
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