Population pharmacokinetics of vancomycin in adult Chinese patients with post-craniotomy meningitis and its application in individualised dosage regimens

Wang, Lin; Wu, Wei; Jiao, Zheng; Lin, Rongfang; Jiang, Changzhen; Huang, Pinfang; Liu, Yiwei; Wang, Changlian

doi:10.1007/s00228-015-1952-6

Cited by 31 publications

(39 citation statements)

References 55 publications

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“…Differences in vancomycin pharmacokinetics have been noted between Asian and Caucasian populations based on two recently published studies (Lin et al, 2015 , 2016 ). To expand this analysis, we first looked at a group of 12 previous studies that examined neonatal populations from various countries.…”

Section: Discussionmentioning

confidence: 99%

Population Pharmacokinetics of Vancomycin in Chinese ICU Neonates: Initial Dosage Recommendations

Liu

Jiao

et al. 2018

Front. Pharmacol.

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The main goal of our study was to characterize the population pharmacokinetics of vancomycin in critically ill Chinese neonates to develop a pharmacokinetic model and investigate factors that have significant influences on the pharmacokinetics of vancomycin in this population. The study population consisted of 80 neonates in the neonatal intensive care unit (ICU) from which 165 trough and peak concentrations of vancomycin were obtained. Nonlinear mixed effect modeling was used to develop a population pharmacokinetic model for vancomycin. The stability and predictive ability of the final model were evaluated based on diagnostic plots, normalized prediction distribution errors and the bootstrap method. Serum creatinine (Scr) and body weight were significant covariates on the clearance of vancomycin. The average clearance was 0.309 L/h for a neonate with Scr of 23.3 μmol/L and body weight of 2.9 kg. No obvious ethnic differences in the clearance of vancomycin were found relative to the earlier studies of Caucasian neonates. Moreover, the established model indicated that in patients with a greater renal clearance status, especially Scr < 15 μmol/L, current guideline recommendations would likely not achieve therapeutic area under the concentration-time curve over 24 h/minimum inhibitory concentration (AUC24h/MIC) ≥ 400. The exceptions to this are British National Formulary (2016–2017), Blue Book (2016) and Neofax (2017). Recommended dose regimens for neonates with different Scr levels and postmenstrual ages were estimated based on Monte Carlo simulations and the established model. These findings will be valuable for developing individualized dosage regimens in the neonatal ICU setting.

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Section: Discussionmentioning

confidence: 99%

Population Pharmacokinetics of Vancomycin in Chinese ICU Neonates: Initial Dosage Recommendations

Liu

Jiao

et al. 2018

Front. Pharmacol.

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“…The guideline of therapeutic drug monitoring for vancomycin recommends that vancomycin dosage should be administered and adjusted individually based on PPK models . PPK models of vancomycin were very common, but most of them incorporated the CLcr as the renal function covariate, which are considered to be defective in estimating renal function. There were only a few PPK models developed optimal dosing regimens according to different CLcr levels .…”

Section: Introductionmentioning

confidence: 99%

A population pharmacokinetic model of vancomycin for dose individualization based on serum cystatin C as a marker of renal function

Liu

Pang

et al. 2019

Journal of Pharmacy and Pharmacology

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Objectives This study aimed to establish a vancomycin population pharmacokinetics (PPK) model based on serum cystatin C and to optimize dosing for achieving targeted steady‐state trough concentrations (Css) of 10–15 and 15–20 mg/l. Methods Patients aged ≥18 years were prospectively enrolled. A vancomycin PPK model was built with glomerular filtration rate (GFR) as a renal covariate estimated by cystatin C. A new group of patients were used for external evaluation. PPK analysis and Monte Carlo simulations were performed using nonlinear mixed effect modelling programme. Key findings Two hundreds of patients with 514 samples were included. The final model was CL (L/h) = (5.07 × (GFR/105.5)0.524 × (AGE/48.5)−0.309 × (WT/60)0.491); V (l) = 46.3. Internal and external evaluations demonstrated good stability and predictability. The average probability of target attainment (PTA) of optimal dosing regimens for targeted Css achieving 10–15 and 15–20 mg/l were 51.2% and 40.6%, respectively. An average PTA ≥71% for targeted concentration of 10–20 mg/l was obtained. Conclusions A vancomycin PPK model with cystatin C as the renal marker has good stability and predictability. The new proposed dosing regimens were predicted to achieve a good PTA.

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“…of infusions Range WT: 40–159 kg; age: 16–97 years; eCL CR : 12–216 mL.min −1 Doses ranging from 500 to 1750 mg.day −1 , no other info available Revilla [ 31 ] Adult ICU patients from Salamanca University Hospital; Spain 191 + 46 TDM data; mostly trough (< −1 h) levels after 3rd dose 66% male; range age: 18–85 years; WT: 45–150 kg; CL CR : 9.5–230 mL.min −1 Intermittent and/or (minority) CoI; doses ranging from 1000 mg q12 h to 1000 mg q24 h for intermittent infusions and mean rate and duration of 57 mg.h −1 and 17.5 h for CoI Sánchez [ 30 ] Adult and geriatric patients from University of California; San Diego, CA, USA 141 + 91 TDM data; single-dose data Age: 55 + 15 years, 28% > 64 years; WT: 73.2 + 17.5 kg; Cr Se : 1.05 + 0.65 mg.dL −1 Average dose was 1628 mg with frequency ranging from q6 h to q48 h Purwonugroho [ 33 ] Adult patients from Ramathibodi Hospital; Bangkok, Thailand 212 + 34 TDM data; single- and multiple-dose data 53% male; age: 66 + 18 years; WT: 58 + 12 kg; eCL CR : 35 + 30 mL.min −1 Dosing as per standard of care, no other information available Lin [ 32 ] Adult Chinese patients with post-craniotomy meningitis from Fujian Medical University; Fuzhou, China 179 + 31 TDM data; through levels after 4th dose 66% male; range age: 18–86 years; range WT: 38–85 kg; range eCL CR : 9.5–217 mL.min −1 Intermittent infusion over 60 min; doses ranging from 1000 to 3000 mg.day −1 Medellín-Garibay [ 34 ] Adult trauma patients from Hospital Universitario Severo Ochoa; Leganés, Spain 118 + 40 TDM data; peak (+ 1 h) and through (− 0.5 h) levels after single and multiple dosing Intermittent infusion over 60 min; doses were mostly 500 mg q12 h and 1000 mg q12 h …”

Section: Resultsmentioning

confidence: 99%

Target-Controlled Continuous Infusion for Antibiotic Dosing: Proof-of-Principle in an In-silico Vancomycin Trial in Intensive Care Unit Patients

2018

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ObjectivesIn this in-silico study, we investigate the clinical utility of target-controlled infusion for antibiotic dosing in an intensive care unit setting using vancomycin as a model compound. We compared target-controlled infusion and adaptive target-controlled infusion, which combines target-controlled infusion with data from therapeutic drug monitoring, with conventional (therapeutic drug monitoring-based) vancomycin dosing strategies.MethodsA clinical trial simulation was conducted. This simulation was based on a comprehensive database of clinical records of intensive care unit patients and a systematic review of currently available population-pharmacokinetic models for vancomycin in intensive care unit patients. Dosing strategies were compared in terms of the probability of achieving efficacious concentrations as well as the potential for inducing toxicity.ResultsAdaptive target-controlled infusion outperforms rule-based dosing guidelines for vancomycin. In the first 48 h of treatment, the probability of target attainment is significantly higher for adaptive target-controlled infusion than for the second-best method (Cristallini). Probability of target attainments of 54 and 72% and 47 and 59% for both methods after 24 and 48 h, respectively. Compared to the Cristallini method, which is characterized by a probability of attaining concentrations above 30 mg.L−1 > 65% in the first few hours of treatment, adaptive target-controlled infusion shows negligible time at risk and a probability of attaining concentrations above 30 mg.L−1 not exceeding 25%. Finally, in contrast to the other methods, the performance of target-controlled infusion is consistent across subgroups within the population.ConclusionsOur study shows that adaptive target-controlled infusion has the potential to become a practical tool for patient-tailored antibiotic dosing in the intensive care unit.Electronic supplementary materialThe online version of this article (10.1007/s40262-018-0643-8) contains supplementary material, which is available to authorized users.

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Population pharmacokinetics of vancomycin in adult Chinese patients with post-craniotomy meningitis and its application in individualised dosage regimens

Abstract: A PPK model was developed to estimate the individual clearance in inpatients receiving intravenously infused VCM and could be used to develop individualised dosing of adult Chinese PCM patients.

Cited by 31 publications

References 55 publications

Population Pharmacokinetics of Vancomycin in Chinese ICU Neonates: Initial Dosage Recommendations

Population Pharmacokinetics of Vancomycin in Chinese ICU Neonates: Initial Dosage Recommendations

A population pharmacokinetic model of vancomycin for dose individualization based on serum cystatin C as a marker of renal function

Target-Controlled Continuous Infusion for Antibiotic Dosing: Proof-of-Principle in an In-silico Vancomycin Trial in Intensive Care Unit Patients

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