Dataset Information

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.

SUBMITTER: Glatard A

PROVIDER: S-EPMC4432143 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Influence of renal function estimation on pharmacokinetic modeling of vancomycin in elderly patients.

Glatard Anaïs A Bourguignon Laurent L Jelliffe Roger W RW Maire Pascal P Neely Michael N MN Goutelle Sylvain S

Antimicrobial agents and chemotherapy 20150309 6

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 elder ...[more]

PMID: 25753640

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Project description:BackgroundVancomycin is widely used to treat gram-positive bacterial infections. However, given significant interpatient variability in its pharmacokinetics, maintaining plasma concentrations is difficult within its characteristically narrow therapeutic window. This is especially challenging in patients with unstable renal function. Thus, the aim of this study was to develop a population pharmacokinetic model for vancomycin that is suitable for Thai patients with variable renal functions, including those with unstable renal function.MethodsData from 213 patients, including 564 blood samples, were retrospectively collected; approximately 70% patients exhibited unstable renal function during vancomycin treatment. The model building group was randomly assigned 108 patients and the remaining 33 patients comprised the validation group. A population pharmacokinetic model was developed that incorporated drug clearance (CL) as a function of time-varying creatine clearance (CrCL). The predictive ability of the resulting population model was evaluated using the validation data set, including its ability to forecast serum concentrations within a Bayesian feedback algorithm.ResultsA 2-compartment model with drug CL values that changed with time-varying CrCL adequately described vancomycin pharmacokinetics in the evaluated heterogeneous patient population with unstable renal function. Vancomycin CL was related to time-varying CrCL as follows: CL (t) = 0.11 + 0.021 × CrCL (t) (CrCL <120 mL/min. Using the population model, Bayesian estimation with at least one measured serum concentration resulted in a forecasting error of small bias (-2.4%) and adequate precision (31.5%).ConclusionsIn hospitals with a high incidence of unstable renal function, incorporating time-varying CrCL with Bayesian estimation and at least one measured drug concentration, along with frequent CrCL monitoring, improves the predictive performance of therapeutic drug monitoring of vancomycin.

Project description:Vancomycin, a glycopeptide antibiotic for the treatment of grampositive infections, is mainly eliminated via glomerular filtration. Thus, its therapeutic effects are affected predominantly by renal function. The aim of this study was to develop a population pharmacokinetic model of vancomycin for Chinese adult patients and to investigate the influence of different renal function descriptors on the predictability of the model. A retrospective analysis was performed based on the blood concentrations of vancomycin in 218 Chinese adult patients. Among these patients, the data from 160 were used to establish the population pharmacokinetic model, and the data from the remaining 58 patients were used for external model validation. A simulation was employed to determine the appropriate initial vancomycin dosage regimens in adult Chinese patients for reaching the target steady-state trough concentrations of 10-15 mg/L and 15-20 mg/L. We developed a one-compartment model with first-order absorption to characterize the concentration-time profile of vancomycin. There was a positive correlation between the body clearance of vancomycin and renal function; both creatinine clearance (CLCr) and age were the covariates that influenced the PK of vancomycin, and the excretion of vancomycin decreased as renal function diminishing with age. The typical clearance (CL) value was 2.829 L/h for 75-year-old patients with CLCr values of 80 mL/min, and the rate constant of CL with the CLCr changing at 1 mL/min was 0.00842. The influence coefficient of age on CL was 0.08143. The external validation results revealed that the current different descriptors of renal function behaved similarly to the predicted performance of the models. In conclusion, the developed model is appropriate for Bayesian dose predictions of vancomycin concentrations in the population of Chinese adult patients. Furthermore, the simulation provides a reference for clinical optimized antibacterial therapy with vancomycin.

Dataset Information

Influence of renal function estimation on pharmacokinetic modeling of vancomycin in elderly patients.

Publications

Influence of renal function estimation on pharmacokinetic modeling of vancomycin in elderly patients.

Similar Datasets

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