Population pharmacokinetics of vancomycin in adult and geriatric patients: comparison of eleven approaches

Sanchez, J.L. Cobo; Domínguez, Arturo R.; Lane, James R.; Anderson, Philip O.; Capparelli, EV; Cornejo-Bravo, José Manuel

doi:10.5414/cpp48525

Cited by 62 publications

(81 citation statements)

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“…In a study performed with 10 anuric patients, nonrenal clearance of vancomycin ranged from 0.23 to 1.40 liters/h (37). Others parameter values are broadly consistent with population studies performed with senior patients (36,38).…”

Section: Discussionsupporting

confidence: 69%

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Influence of Renal Function Estimation on Pharmacokinetic Modeling of Vancomycin in Elderly Patients

Glatard

Bourguignon

Jelliffe³

et al. 2015

Antimicrob Agents Chemother

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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 1.73 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.

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Section: Discussionsupporting

confidence: 69%

“…The predictive performance of the model as well as that of 10 other PK methods was then evaluated in an independent data set of 95 patients with a mean age of 50 Ϯ 17 years (36). The 10 other methods consisted of regression equations predicting vancomycin body clearance and, for some of them, volume of distribution.…”

Section: Discussionmentioning

confidence: 99%

Influence of Renal Function Estimation on Pharmacokinetic Modeling of Vancomycin in Elderly Patients

Glatard

Bourguignon

Jelliffe³

et al. 2015

Antimicrob Agents Chemother

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“…In this cohort of patients over 80, the best structural model was found to be a two-compartment model, as in most of the studies carried out in adults (9,(18)(19)(20)(21)(22)(23).…”

Section: Discussionmentioning

confidence: 90%

Pharmacokinetics of Vancomycin in Elderly Patients Aged over 80 Years

Bourguignon

Cazaubon

Debeurme

et al. 2016

Antimicrob Agents Chemother

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cSince the 1950s, vancomycin has remained a reference treatment for severe infections caused by Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus. Vancomycin is a nephrotoxic and ototoxic drug mainly eliminated through the kidneys. It has a large interindividual pharmacokinetic variability, which justifies monitoring its plasma concentrations in patients. This is especially important in patients aged over 80 years, who frequently have renal impairment. However, the pharmacokinetics of vancomycin in this population is very poorly described in the literature. The objective of this work was to propose a model able to predict the pharmacokinetics of vancomycin in very elderly people. First, a population pharmacokinetic model was carried out using the algorithm NPAG (nonparametric adaptive grid) on a database of 70 hospitalized patients aged over 80 years and treated with vancomycin. An external validation then was performed on 41 patients, and the predictive capabilities of the model were assessed. The model had two compartments and six parameters. Body weight and creatinine clearance significantly influenced vancomycin volume of distribution and body clearance, respectively. The means (؎ standard deviations) of vancomycin volume of distribution and clearance were 36.3 ؎ 15.2 liter and 2.0 ؎ 0.9 liter/h, respectively. In the validation group, the bias and precision were ؊0.75 mg/liter and 8.76 mg/liter for population predictions and ؊0.39 mg/liter and 2.68 mg/ liter for individual predictions. In conclusion, a pharmacokinetic model of vancomycin in a very elderly population has been created and validated for predicting plasma concentrations of vancomycin. Vancomycin is a glycopeptide antibacterial that is widely used for the treatment of serious Gram-positive infections, notably those caused by methicillin-resistant Staphylococcus aureus (MRSA) (1). With the widespread appearance of resistant pathogens such as MRSA, the use of vancomycin has dramatically increased since the early 1980s. The activity of vancomycin is related to an inhibition of the biosynthesis of the bacterial cell wall. The molecule diffuses into the cell wall and binds to the disaccharide pentapeptides, preventing their polymerization and leading to discontinuation of the synthesis of peptidoglycan of the bacterial cell wall.The concentration-effect relationship of vancomycin has been characterized, and the pharmacokinetic (PK)-pharmacodynamic parameter that best describes the efficacy is the ratio of the area under the serum drug concentration-time curve to the MIC (AUC/MIC) (2, 3). Regarding toxicity, it has been shown that vancomycin nephrotoxicity is dose dependent and linked to vancomycin trough concentration (4). As vancomycin elimination is mainly renal, patients with renal impairment are at risk of overexposure and toxicity. As a consequence, a careful monitoring of vancomycin serum concentrations is recommended (5, 6) to optimize efficacy and prevent toxicity.Several methods can be used to individualize dosage ...

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“…17 Patients were categorized into two groups according to whether age was <65 years or not. 18 The median body weight of subjects in our data set (60 kg) was used as the cutoff value to divide patients into two categories. The predictive 141 Caucasoid…”

Section: Bayesian Forecastingmentioning

confidence: 99%

Predictive performance of reported population pharmacokinetic models of vancomycin in Chinese adult patients

Deng

Liu

et al. 2013

J Clin Pharm Ther

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SUMMARYWhat is known and objective: There are numerous studies on population pharmacokinetics of vancomycin in adult patients. However, there is no such research for Chinese adult patients. This study was conducted to evaluate the predictive performance of reported population pharmacokinetic models of vancomycin in Chinese adult patients and to identify some models appropriate for our population. Methods: A literature search was conducted in PubMed to obtain the population pharmacokinetic models of vancomycin published between December 2010 and September 2012. The models were assessed using concentration data collected from Chinese patients for external validation. Models with relatively poor predictability were excluded from further analysis. The performance of the remaining models was evaluated in patients with different levels of creatinine clearance, age, body weight and sex by Bayesian method. This method was also used to compare the predictive performance based on peak concentration and trough concentration and the predictability based on different number of observed concentrations. Results: One hundred and sixty-five blood concentrations from 72 Chinese adult patients were collected retrospectively to serve as the test data set. The evaluated models included all those reported in the seven publications reviewed by Marsot et al. and three other studies published after December 2010. Three models with poor performance on external validation were excluded from the next Bayesian analysis. The distribution of covariates in the model building data set had an important effect on prediction. The predictability based on peak/trough concentration was similar among the evaluated models, and no significant difference was found using our data set except for Roberts' model. As expected, an increased number of samples improved the performance of the Bayesian prediction. What is new and conclusion: With our data set, the performance of the evaluated models varied. The characteristics of the patient population and distribution of covariates should be given more consideration when choosing a model to predict blood concentrations. The model developed by Purwonugroho et al. using a data set from patients similar to ours is appropriate for Bayesian dose predictions for vancomycin concentrations in our population of Chinese adult patients. WHAT IS KNOWN AND OBJECTIVEVancomycin is a glycopeptide antibiotic, with time-dependent bacterial killing effect, which is used for therapy of infections caused by penicillinase-producing Staphylococcus aureus, especially methicillin-resistant Staphylococcus aureus (MRSA), Staphylococcus epidermis and Enterococcus faecalis.

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Population pharmacokinetics of vancomycin in adult and geriatric patients: comparison of eleven approaches

Cited by 62 publications

References 0 publications

Influence of Renal Function Estimation on Pharmacokinetic Modeling of Vancomycin in Elderly Patients

Influence of Renal Function Estimation on Pharmacokinetic Modeling of Vancomycin in Elderly Patients

Pharmacokinetics of Vancomycin in Elderly Patients Aged over 80 Years

Predictive performance of reported population pharmacokinetic models of vancomycin in Chinese adult patients

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