Improvement of Predictivity of Teicoplanin Serum Trough Concentrations at Steady State Calculated by Vancomycin Pharmacokinetic Parameter

Kobayashi, Ryo; Otomo, Shinya; Shiba, Yusuke; Ebinuma, Keiichi; Sudoh, Toshiaki

doi:10.1248/yakushi.16-00025

Cited by 3 publications

(2 citation statements)

References 22 publications

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“…However, the target value of AUC 24 /MIC for teicoplanin did not have been extensively studied. Clinical efficacy also could be assessed by the teicoplanin trough concentration (Harding and Sorgel, 2000;Kobayashi et al, 2016), and the trough concentration of 10-30 mg/L had a guarantee for most infections as previously reported. In order to reach the trough level, children with different renal functions required different loading and maintenance doses because of their different teicoplanin CL.…”

Section: Discussionmentioning

confidence: 87%

Population Pharmacokinetics and Dosage Optimization of Teicoplanin in Children With Different Renal Functions

Gao

et al. 2020

Front. Pharmacol.

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Objective: The purposes of our study were to investigate the population pharmacokinetics of teicoplanin in Chinese children with different renal functions and to propose the appropriate dosing regimen for these pediatric patients.Methods: We performed a prospective pharmacokinetic research on children aged 0-10 years, with different renal functions. The population pharmacokinetics model of teicoplanin was developed using NLME program. The individualized optimal dosage regimen was proposed on the basis of the obtained population pharmacokinetics parameters.Results: To achieve the target trough level of 10-30 mg/L, optimal dosing regimen for children with different renal functions are predicted as follows based on the population PK simulations: children with moderate renal insufficiency need three loading doses of 6 mg/ kg q12h followed by a maintenance dose of 5 mg/kg qd; children with mild renal insufficiency require three loading doses of 12 mg/kg q12h followed by a maintenance dose of 8 mg/kg qd; children with normal or augmented renal function should be given three loading doses of 12 mg/kg q12h followed by a maintenance doses of 10 mg/kg qd. Conclusion:The first study on the population pharmacokinetics of teicoplanin in Chinese children with different renal functions was performed. Individualized dosing regimen was recommended for different renal function groups based on population PK model prediction.

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Section: Discussionmentioning

confidence: 87%

Population Pharmacokinetics and Dosage Optimization of Teicoplanin in Children With Different Renal Functions

Gao

et al. 2020

Front. Pharmacol.

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“…6 So far, some vancomycin concentration prediction algorithms were developed using linear regression analysis in adult and pediatric patients. 9,10 The rapidly developing machine learning methods can help promote data-driven estimation when predicting from multiple variables and capture non-linear variable relations to achieve high accuracy in predicting clinical outcomes. 11,12 This article aims to establish an optimal model to predict vancomycin trough concentrations in pediatric patients by using machine learning methods.…”

Section: Introductionmentioning

confidence: 99%

An Ensemble Model for Prediction of Vancomycin Trough Concentrations in Pediatric Patients

Huang¹,

Yu²,

Bu³

et al. 2021

DDDT

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Purpose This study aimed to establish an optimal model to predict vancomycin trough concentrations by using machine learning. Patients and Methods We enrolled 407 pediatric patients (age < 18 years) who received vancomycin intravenously and underwent therapeutic drug monitoring from June 2013 to April 2020 at Xinhua Hospital affiliated to Shanghai Jiaotong University School of Medicine. The median (interquartile range) age and weight of the patients were 2 (0.63–5) years and 12 (7.8–19) kg. Vancomycin trough concentrations were considered as the target variable, and eight different algorithms were used for predictive performance comparison. The whole dataset (407 cases) was divided into training group and testing group at the ratio of 80%: 20%, which were 325 and 82 cases, respectively. Results Ultimately, five algorithms (XGBoost, GBRT, Bagging, ExtraTree and decision tree) with high R 2 (0.657, 0.514, 0.468, 0.425 and 0.450, respectively) were selected and further ensembled to establish the final model and achieve an optimal result. For missing data, through filling the missing values and model ensemble, we obtained R 2 =0.614, MAE=3.32, MSE=24.39, RMSE=4.94 and a prediction accuracy of 51.22% (predicted trough concentration within ±30% of the actual trough concentration). In comparison with the pharmacokinetic models ( R 2 =0.3), the machine learning model works better in model fitting and has better prediction accuracy. Conclusion Therefore, the ensemble model is useful for the vancomycin concentration prediction, especially in the population of children with great individual variation. As machine learning methods evolve, the clinical value of the ensemble model will be demonstrated in the clinical practice.

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Retrospective analysis of relationships among the dose regimen, trough concentration, efficacy, and safety of teicoplanin in Chinese patients with moderate–severe Gram-positive infections

Zhou¹,

Gao²,

Cao³

et al. 2018

IDR

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ObjectivesTeicoplanin, an antibiotic, has poor clinical efficacy when using the current drug label’s recommended regimen, which is approved by the China Food and Drug Administration. This study explores the appropriate loading and maintenance doses of teicoplanin and evaluates the therapeutic target of teicoplanin trough concentration (minimum concentration [Cmin]).Subjects and methodsAll patients treated with teicoplanin from February 2015 to August 2016 at Zhengzhou Central Hospital were screened for enrollment. A total of 113 subjects were included and then divided into four groups: A (received three to six doses at a loading dose of 400 mg at 12-hour intervals, followed by maintenance dosing of 400 mg/day), B (received three doses at a loading dose of 400 mg at 12-hour intervals, followed by maintenance dosing of 400 mg/day), C (received two doses at a loading dose of 400 mg at 12-hour intervals, followed by maintenance dosing of 200 mg/day), and D (received one to three doses at a loading dose of 400 mg at 12-hour intervals, followed by maintenance dosing of 200 mg/day). Cmin values of teicoplanin were detected with high-performance liquid chromatography on day 4, 30 minutes before maintenance-dose administration. Teicoplanin Cmin, efficacy, and safety were compared among the four groups.ResultsMean Cmin differed significantly among the four groups (A, 18.11±6.37 mg/L; B, 15.91±4.94 mg/L; C, 17.06±5.66 mg/L; D, 11.97±3.76 mg/L) (P<0.001), with creatinine clearance of 89.62 (53.72–162.48), 49.66 (40.69–59.64), 27.17 (9.7–39.45), and 96.6 (17.63–394.73) mL/min, respectively. The ratio of loading dose for 3 days to creatinine clearance and serum Cmin were significantly correlated (R=0.59, P<0.001). The correlation between the estimated probability of success and teicoplanin Cmin was assessed using binary logistic regression (OR 2.049, P<0.001). Hepatotoxicity- and nephrotoxicity-incidence rates did not significantly differ among the four groups (P=0.859 and P=0.949, respectively).ConclusionA loading dose of 400 mg at 12-hour intervals three to six times is needed to achieve the early target range (15–20 mg/L) and improve the clinical efficacy rate for normal-renal-function patients. It is urgently necessary to amend the drug label for the recommended regimen.

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Improvement of Predictivity of Teicoplanin Serum Trough Concentrations at Steady State Calculated by Vancomycin Pharmacokinetic Parameter

Cited by 3 publications

References 22 publications

Population Pharmacokinetics and Dosage Optimization of Teicoplanin in Children With Different Renal Functions

Population Pharmacokinetics and Dosage Optimization of Teicoplanin in Children With Different Renal Functions

An Ensemble Model for Prediction of Vancomycin Trough Concentrations in Pediatric Patients

Retrospective analysis of relationships among the dose regimen, trough concentration, efficacy, and safety of teicoplanin in Chinese patients with moderate–severe Gram-positive infections

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Improvement of Predictivity of Teicoplanin Serum Trough Concentrations at Steady State Calculated by Vancomycin Pharmacokinetic Parameter

Cited by 3 publications

References 22 publications

Population Pharmacokinetics and Dosage Optimization of Teicoplanin in Children With Different Renal Functions

Population Pharmacokinetics and Dosage Optimization of Teicoplanin in Children With Different Renal Functions

An Ensemble Model for Prediction of Vancomycin Trough Concentrations in Pediatric Patients

Retrospective analysis of relationships among the dose regimen, trough concentration, efficacy, and safety of teicoplanin in Chinese patients with moderate&ndash;severe Gram-positive infections

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Retrospective analysis of relationships among the dose regimen, trough concentration, efficacy, and safety of teicoplanin in Chinese patients with moderate–severe Gram-positive infections