title: Influence of renal function estimation on pharmacokinetic modeling of vancomycin in elderly patients.
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.
authors.affiliation: Service pharmaceutique-ADCAPT, Groupement Hospitalier de Gériatrie, Hospices Civils de Lyon, Lyon, France.
authors.forename: Anaïs
authors.initials: A
authors.lastname: Glatard
authors.affiliation: Service pharmaceutique-ADCAPT, Groupement Hospitalier de Gériatrie, Hospices Civils de Lyon, Lyon, France Laboratoire de Biométrie et Biologie Evolutive, CNRS UMR 5558, Université Lyon 1, Villeurbanne, France.
authors.forename: Laurent
authors.initials: L
authors.lastname: Bourguignon
authors.affiliation: Laboratory of Applied Pharmacokinetics, USC School of Medicine, Los Angeles, California, USA.
authors.forename: Roger W
authors.initials: RW
authors.lastname: Jelliffe
authors.affiliation: Service pharmaceutique-ADCAPT, Groupement Hospitalier de Gériatrie, Hospices Civils de Lyon, Lyon, France Laboratoire de Biométrie et Biologie Evolutive, CNRS UMR 5558, Université Lyon 1, Villeurbanne, France.
authors.forename: Pascal
authors.initials: P
authors.lastname: Maire
authors.affiliation: Laboratory of Applied Pharmacokinetics, USC School of Medicine, Los Angeles, California, USA sylvain.goutelle@chu-lyon.fr mneely@usc.edu.
authors.forename: Michael N
authors.initials: MN
authors.lastname: Neely
authors.affiliation: Service pharmaceutique-ADCAPT, Groupement Hospitalier de Gériatrie, Hospices Civils de Lyon, Lyon, France Laboratoire de Biométrie et Biologie Evolutive, CNRS UMR 5558, Université Lyon 1, Villeurbanne, France Faculté de Pharmacie de Lyon-ISPB, Université Lyon 1, Lyon, France sylvain.goutelle@chu-lyon.fr mneely@usc.edu.
authors.forename: Sylvain
authors.initials: S
authors.lastname: Goutelle
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D005919:Glomerular Filtration Rate / Q000502:physiology; D006801:Humans; D007677:Kidney Function Tests; D008297:Male; D008962:Models, Theoretical; D012189:Retrospective Studies; D014640:Vancomycin / Q000493:pharmacokinetics*
chemical_list: D014640:Vancomycin