Influence of Renal Function Estimation on Pharmacokinetic Modeling of Vancomycin in Elderly Patients
Vancomycin is a renally excreted drug, and its body clearance correlates with creatinine clearance. However, the renal function estimation equation that best predicts vancomycin clearance has not been established yet. The objective of this study was to compare the abilities of different renal functi...
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| Published in | Antimicrobial agents and chemotherapy Vol. 59; no. 6; pp. 2986 - 2994 |
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| Main Authors | , , , , , |
| Format | Journal Article |
| Language | English |
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American Society for Microbiology
01.06.2015
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| Abstract | Vancomycin is a renally excreted drug, and its body clearance correlates with creatinine clearance. However, the renal function estimation equation that best predicts vancomycin clearance has not been established yet. The objective of this study was to compare the abilities of different renal function estimation equations to describe vancomycin pharmacokinetics in elderly patients. The NPAG algorithm was used to perform population pharmacokinetic analysis of vancomycin concentrations in 78 elderly patients. Six pharmacokinetic models of vancomycin clearance were built, based on the following equations: Cockcroft-Gault (CG), Jelliffe (JEL), Modification of Diet in Renal Disease (MDRD), Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) (both in milliliters per minute per 1.73 m
2
), and modified MDRD and CKD-EPI equations (both in milliliters per minute). Goodness-of-fit and predictive performances of the six PK models were compared in a learning set (58 subjects) and a validation set (20 patients). Final analysis was performed to estimate population parameters in the entire population. In the learning step, the MDRD-based model best described the data, but the CG- and JEL-based models were the least biased. The mean weighted errors of prediction were significantly different between the six models (
P
= 0.0071). In the validation group, predictive performances were not significantly different. However, the use of a renal function estimation equation different from that used in the model building could significantly alter predictive performance. The final analysis showed important differences in parameter distributions and AUC estimation across the six models. This study shows that methods used to estimate renal function should not be considered interchangeable for pharmacokinetic modeling and model-based estimation of vancomycin concentrations in elderly patients. |
|---|---|
| AbstractList | Vancomycin is a renally excreted drug, and its body clearance correlates with creatinine clearance. However, the renal function estimation equation that best predicts vancomycin clearance has not been established yet. The objective of this study was to compare the abilities of different renal function estimation equations to describe vancomycin pharmacokinetics in elderly patients. The NPAG algorithm was used to perform population pharmacokinetic analysis of vancomycin concentrations in 78 elderly patients. Six pharmacokinetic models of vancomycin clearance were built, based on the following equations: Cockcroft-Gault (CG), Jelliffe (JEL), Modification of Diet in Renal Disease (MDRD), Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) (both in milliliters per minute per 1.73 m2), and modified MDRD and CKD-EPI equations (both in milliliters per minute). Goodness-of-fit and predictive performances of the six PK models were compared in a learning set (58 subjects) and a validation set (20 patients). Final analysis was performed to estimate population parameters in the entire population. In the learning step, the MDRD-based model best described the data, but the CG- and JEL-based models were the least biased. The mean weighted errors of prediction were significantly different between the six models (P = 0.0071). In the validation group, predictive performances were not significantly different. However, the use of a renal function estimation equation different from that used in the model building could significantly alter predictive performance. The final analysis showed important differences in parameter distributions and AUC estimation across the six models. This study shows that methods used to estimate renal function should not be considered interchangeable for pharmacokinetic modeling and model-based estimation of vancomycin concentrations in elderly patients. Vancomycin is a renally excreted drug, and its body clearance correlates with creatinine clearance. However, the renal function estimation equation that best predicts vancomycin clearance has not been established yet. The objective of this study was to compare the abilities of different renal function estimation equations to describe vancomycin pharmacokinetics in elderly patients. The NPAG algorithm was used to perform population pharmacokinetic analysis of vancomycin concentrations in 78 elderly patients. Six pharmacokinetic models of vancomycin clearance were built, based on the following equations: Cockcroft-Gault (CG), Jelliffe (JEL), Modification of Diet in Renal Disease (MDRD), Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) (both in milliliters per minute per 1.73 m(2)), and modified MDRD and CKD-EPI equations (both in milliliters per minute). Goodness-of-fit and predictive performances of the six PK models were compared in a learning set (58 subjects) and a validation set (20 patients). Final analysis was performed to estimate population parameters in the entire population. In the learning step, the MDRD-based model best described the data, but the CG- and JEL-based models were the least biased. The mean weighted errors of prediction were significantly different between the six models (P = 0.0071). In the validation group, predictive performances were not significantly different. However, the use of a renal function estimation equation different from that used in the model building could significantly alter predictive performance. The final analysis showed important differences in parameter distributions and AUC estimation across the six models. This study shows that methods used to estimate renal function should not be considered interchangeable for pharmacokinetic modeling and model-based estimation of vancomycin concentrations in elderly patients.Vancomycin is a renally excreted drug, and its body clearance correlates with creatinine clearance. However, the renal function estimation equation that best predicts vancomycin clearance has not been established yet. The objective of this study was to compare the abilities of different renal function estimation equations to describe vancomycin pharmacokinetics in elderly patients. The NPAG algorithm was used to perform population pharmacokinetic analysis of vancomycin concentrations in 78 elderly patients. Six pharmacokinetic models of vancomycin clearance were built, based on the following equations: Cockcroft-Gault (CG), Jelliffe (JEL), Modification of Diet in Renal Disease (MDRD), Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) (both in milliliters per minute per 1.73 m(2)), and modified MDRD and CKD-EPI equations (both in milliliters per minute). Goodness-of-fit and predictive performances of the six PK models were compared in a learning set (58 subjects) and a validation set (20 patients). Final analysis was performed to estimate population parameters in the entire population. In the learning step, the MDRD-based model best described the data, but the CG- and JEL-based models were the least biased. The mean weighted errors of prediction were significantly different between the six models (P = 0.0071). In the validation group, predictive performances were not significantly different. However, the use of a renal function estimation equation different from that used in the model building could significantly alter predictive performance. The final analysis showed important differences in parameter distributions and AUC estimation across the six models. This study shows that methods used to estimate renal function should not be considered interchangeable for pharmacokinetic modeling and model-based estimation of vancomycin concentrations in elderly patients. Vancomycin is a renally excreted drug, and its body clearance correlates with creatinine clearance. However, the renal function estimation equation that best predicts vancomycin clearance has not been established yet. The objective of this study was to compare the abilities of different renal function estimation equations to describe vancomycin pharmacokinetics in elderly patients. The NPAG algorithm was used to perform population pharmacokinetic analysis of vancomycin concentrations in 78 elderly patients. Six pharmacokinetic models of vancomycin clearance were built, based on the following equations: Cockcroft-Gault (CG), Jelliffe (JEL), Modification of Diet in Renal Disease (MDRD), Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) (both in milliliters per minute per 1.73 m 2 ), and modified MDRD and CKD-EPI equations (both in milliliters per minute). Goodness-of-fit and predictive performances of the six PK models were compared in a learning set (58 subjects) and a validation set (20 patients). Final analysis was performed to estimate population parameters in the entire population. In the learning step, the MDRD-based model best described the data, but the CG- and JEL-based models were the least biased. The mean weighted errors of prediction were significantly different between the six models ( P = 0.0071). In the validation group, predictive performances were not significantly different. However, the use of a renal function estimation equation different from that used in the model building could significantly alter predictive performance. The final analysis showed important differences in parameter distributions and AUC estimation across the six models. This study shows that methods used to estimate renal function should not be considered interchangeable for pharmacokinetic modeling and model-based estimation of vancomycin concentrations in elderly patients. Vancomycin is a renally excreted drug, and its body clearance correlates with creatinine clearance. However, the renal function estimation equation that best predicts vancomycin clearance has not been established yet. The objective of this study was to compare the abilities of different renal function estimation equations to describe vancomycin pharmacokinetics in elderly patients. The NPAG algorithm was used to perform population pharmacokinetic analysis of vancomycin concentrations in 78 elderly patients. Six pharmacokinetic models of vancomycin clearance were built, based on the following equations: CockcroftGault (CG), Jelliffe (JEL), Modification of Diet in Renal Disease (MDRD), Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) (both in milliliters per minute per 1.73m(2)), and modified MDRD and CKD-EPI equations (both in milliliters per minute). Goodness-of-fit and predictive performances of the six PK models were compared in a learning set (58 subjects) and a validation set (20 patients). Final analysis was performed to estimate population parameters in the entire population. In the learning step, the MDRD-based model best described the data, but the CG-and JEL-based models were the least biased. The mean weighted errors of prediction were significantly different between the six models (P = 0.0071). In the validation group, predictive performances were not significantly different. However, the use of a renal function estimation equation different from that used in the model building could significantly alter predictive performance. The final analysis showed important differences in parameter distributions and AUC estimation across the six models. This study shows that methods used to estimate renal function should not be considered interchangeable for pharmacokinetic modeling and model-based estimation of vancomycin concentrations in elderly patients. Vancomycin is a renally excreted drug, and its body clearance correlates with creatinine clearance. However, the renal function estimation equation that best predicts vancomycin clearance has not been established yet. The objective of this study was to compare the abilities of different renal function estimation equations to describe vancomycin pharmacokinetics in elderly patients. The NPAG algorithm was used to perform population pharmacokinetic analysis of vancomycin concentrations in 78 elderly patients. Six pharmacokinetic models of vancomycin clearance were built, based on the following equations: Cockcroft-Gault (CG), Jelliffe (JEL), Modification of Diet in Renal Disease (MDRD), Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) (both in milliliters per minute per 1.73 m(2)), and modified MDRD and CKD-EPI equations (both in milliliters per minute). Goodness-of-fit and predictive performances of the six PK models were compared in a learning set (58 subjects) and a validation set (20 patients). Final analysis was performed to estimate population parameters in the entire population. In the learning step, the MDRD-based model best described the data, but the CG- and JEL-based models were the least biased. The mean weighted errors of prediction were significantly different between the six models (P = 0.0071). In the validation group, predictive performances were not significantly different. However, the use of a renal function estimation equation different from that used in the model building could significantly alter predictive performance. The final analysis showed important differences in parameter distributions and AUC estimation across the six models. This study shows that methods used to estimate renal function should not be considered interchangeable for pharmacokinetic modeling and model-based estimation of vancomycin concentrations in elderly patients. |
| Author | Neely, Michael N. Glatard, Anaïs Jelliffe, Roger W. Bourguignon, Laurent Maire, Pascal Goutelle, Sylvain |
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| Cites_doi | 10.2165/11596390-000000000-00000 10.1128/AAC.05634-11 10.1159/000180580 10.1053/j.ajkd.2012.06.016 10.1097/00007691-199410000-00013 10.1128/AAC.25.4.433 10.1111/imj.12036 10.1093/ndt/gfm289 10.2146/ajhp080071 10.1016/j.addr.2014.05.016 10.1002/phar.1282 10.1002/j.1552-4604.1993.tb01922.x 10.1111/j.1365-2710.2008.01015.x 10.1681/ASN.2004070549 10.1159/000065221 10.7326/0003-4819-94-3-343 10.7326/0003-4819-150-9-200905050-00006 10.1136/bmjopen-2013-003343 10.5414/CPP48525 10.1097/00007691-199804000-00003 10.1177/0310057X1404200203 10.1345/aph.1Q757 10.1097/00007691-199003000-00017 10.7326/0003-4819-145-4-200608150-00004 10.1046/j.1365-2389.2003.51330.x 10.1128/AAC.01653-13 10.2146/ajhp060047 10.1373/clinchem.2006.077180 10.7326/0003-4819-130-6-199903160-00002 10.1136/bmjopen-2013-002686 10.1038/ki.2011.322 10.1128/AAC.34.6.1165 10.1007/s10928-013-9302-8 10.1128/AAC.32.6.848 10.2146/ajhp080434 10.1053/j.ajkd.2009.03.008 10.1038/clpt.1991.208 |
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| Copyright | Copyright © 2015, American Society for Microbiology. All Rights Reserved. Distributed under a Creative Commons Attribution 4.0 International License Copyright © 2015, American Society for Microbiology. All Rights Reserved. 2015 American Society for Microbiology |
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| Snippet | Vancomycin is a renally excreted drug, and its body clearance correlates with creatinine clearance. However, the renal function estimation equation that best... |
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| SubjectTerms | Aged Aged, 80 and over Female Glomerular Filtration Rate - physiology Humans Kidney Function Tests Life Sciences Male Models, Theoretical Pharmacology Retrospective Studies Vancomycin Vancomycin - pharmacokinetics |
| Title | Influence of Renal Function Estimation on Pharmacokinetic Modeling of Vancomycin in Elderly Patients |
| URI | https://www.ncbi.nlm.nih.gov/pubmed/25753640 https://journals.asm.org/doi/10.1128/AAC.04132-14 https://www.proquest.com/docview/1681260862 https://www.proquest.com/docview/1701480861 https://univ-lyon1.hal.science/hal-02044772 https://pubmed.ncbi.nlm.nih.gov/PMC4432143 |
| Volume | 59 |
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