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Population pharmacokinetics of unbound and total teicoplanin in critically ill pediatric patients

(2021) CLINICAL PHARMACOKINETICS. 60(3). p.353-363
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Abstract
Background and Objectives Teicoplanin is a highly protein-bound antibiotic, increasingly used to treat serious Gram-positive infections in critically ill children. Maturational and pathophysiological intensive care unit-related changes often lead to altered pharmacokinetics. In this study, the objectives were to develop a pediatric population-pharmacokinetic model of unbound and total teicoplanin concentrations, to investigate the impact of plasma albumin levels and renal function on teicoplanin pharmacokinetics, and to evaluate the efficacy of the current weight-based dosing regimen. Methods An observational pharmacokinetic study was performed and blood samples were collected for quantification of unbound and total concentrations of teicoplanin after the first dose and in assumed steady-state conditions. A population-pharmacokinetic analysis was conducted using a standard sequential approach and Monte Carlo simulations were performed for a probability of target attainment analysis using previously published pharmacokinetic-pharmacodynamic targets. Results A two-compartment model with allometric scaling of pharmacokinetic parameters and non-linear plasma protein binding best described the data. Neither the inclusion of albumin nor the renal function significantly improved the model and no other covariates were supported for inclusion in the final model. The probability of target attainment analysis showed that the standard dosing regimen does not satisfactory attain the majority of the proposed targets. Conclusions We successfully characterized the pharmacokinetics of unbound and total teicoplanin in critically ill pediatric patients. The highly variable unbound fraction of teicoplanin could not be predicted using albumin levels, which may support the use of therapeutic drug monitoring of unbound concentrations. Poor target attainment was shown for the most commonly used dosing regimen, regardless of the pharmacokinetic-pharmacodynamic target evaluated.
Keywords
Pharmacology (medical), Pharmacology, SERUM CREATININE, PROTEIN-BINDING, CHILDREN, VANCOMYCIN, QUANTIFICATION, OPTIMIZATION, CLEARANCE, THERAPY, MODELS, PLASMA

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MLA
Aulin, L. B. S., et al. “Population Pharmacokinetics of Unbound and Total Teicoplanin in Critically Ill Pediatric Patients.” CLINICAL PHARMACOKINETICS, vol. 60, no. 3, 2021, pp. 353–63, doi:10.1007/s40262-020-00945-4.
APA
Aulin, L. B. S., De Paepe, P., Dhont, E., de Jaeger, A., Vande Walle, J., Vandenberghe, W., … De Cock, P. (2021). Population pharmacokinetics of unbound and total teicoplanin in critically ill pediatric patients. CLINICAL PHARMACOKINETICS, 60(3), 353–363. https://doi.org/10.1007/s40262-020-00945-4
Chicago author-date
Aulin, L. B. S., Peter De Paepe, Evelyn Dhont, Annik de Jaeger, Johan Vande Walle, Wim Vandenberghe, B. C. McWhinney, J. P. J. Ungerer, J. G. C. van Hasselt, and Pieter De Cock. 2021. “Population Pharmacokinetics of Unbound and Total Teicoplanin in Critically Ill Pediatric Patients.” CLINICAL PHARMACOKINETICS 60 (3): 353–63. https://doi.org/10.1007/s40262-020-00945-4.
Chicago author-date (all authors)
Aulin, L. B. S., Peter De Paepe, Evelyn Dhont, Annik de Jaeger, Johan Vande Walle, Wim Vandenberghe, B. C. McWhinney, J. P. J. Ungerer, J. G. C. van Hasselt, and Pieter De Cock. 2021. “Population Pharmacokinetics of Unbound and Total Teicoplanin in Critically Ill Pediatric Patients.” CLINICAL PHARMACOKINETICS 60 (3): 353–363. doi:10.1007/s40262-020-00945-4.
Vancouver
1.
Aulin LBS, De Paepe P, Dhont E, de Jaeger A, Vande Walle J, Vandenberghe W, et al. Population pharmacokinetics of unbound and total teicoplanin in critically ill pediatric patients. CLINICAL PHARMACOKINETICS. 2021;60(3):353–63.
IEEE
[1]
L. B. S. Aulin et al., “Population pharmacokinetics of unbound and total teicoplanin in critically ill pediatric patients,” CLINICAL PHARMACOKINETICS, vol. 60, no. 3, pp. 353–363, 2021.
@article{8697476,
  abstract     = {{Background and Objectives Teicoplanin is a highly protein-bound antibiotic, increasingly used to treat serious Gram-positive infections in critically ill children. Maturational and pathophysiological intensive care unit-related changes often lead to altered pharmacokinetics. In this study, the objectives were to develop a pediatric population-pharmacokinetic model of unbound and total teicoplanin concentrations, to investigate the impact of plasma albumin levels and renal function on teicoplanin pharmacokinetics, and to evaluate the efficacy of the current weight-based dosing regimen. Methods An observational pharmacokinetic study was performed and blood samples were collected for quantification of unbound and total concentrations of teicoplanin after the first dose and in assumed steady-state conditions. A population-pharmacokinetic analysis was conducted using a standard sequential approach and Monte Carlo simulations were performed for a probability of target attainment analysis using previously published pharmacokinetic-pharmacodynamic targets. Results A two-compartment model with allometric scaling of pharmacokinetic parameters and non-linear plasma protein binding best described the data. Neither the inclusion of albumin nor the renal function significantly improved the model and no other covariates were supported for inclusion in the final model. The probability of target attainment analysis showed that the standard dosing regimen does not satisfactory attain the majority of the proposed targets. Conclusions We successfully characterized the pharmacokinetics of unbound and total teicoplanin in critically ill pediatric patients. The highly variable unbound fraction of teicoplanin could not be predicted using albumin levels, which may support the use of therapeutic drug monitoring of unbound concentrations. Poor target attainment was shown for the most commonly used dosing regimen, regardless of the pharmacokinetic-pharmacodynamic target evaluated.}},
  author       = {{Aulin, L. B. S. and De Paepe, Peter and Dhont, Evelyn and de Jaeger, Annik and Vande Walle, Johan and Vandenberghe, Wim and McWhinney, B. C. and Ungerer, J. P. J. and van Hasselt, J. G. C. and De Cock, Pieter}},
  issn         = {{0312-5963}},
  journal      = {{CLINICAL PHARMACOKINETICS}},
  keywords     = {{Pharmacology (medical),Pharmacology,SERUM CREATININE,PROTEIN-BINDING,CHILDREN,VANCOMYCIN,QUANTIFICATION,OPTIMIZATION,CLEARANCE,THERAPY,MODELS,PLASMA}},
  language     = {{eng}},
  number       = {{3}},
  pages        = {{353--363}},
  title        = {{Population pharmacokinetics of unbound and total teicoplanin in critically ill pediatric patients}},
  url          = {{http://dx.doi.org/10.1007/s40262-020-00945-4}},
  volume       = {{60}},
  year         = {{2021}},
}

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