Population pharmacokinetics of teicoplanin in children
V Ramos-Martín1, S Paulus2, S Siner2
1Department of Women's and Children's Health, Institute of Translational Medicine, University of Liverpool, Liverpool, United Kingdom Molecular and Clinical Pharmacology Department, Institute of Translational Medicine, University of Liverpool, Liverpool, United Kingdom.
Insights
Pediatric teicoplanin pharmacokinetics (PK) are highly variable, with current dosing often failing to achieve therapeutic concentrations. Routine therapeutic drug monitoring is recommended for children to ensure optimal teicoplanin treatment effectiveness.
Area of Science:
- Pharmacology
- Pediatric Medicine
- Infectious Diseases
Background:
- Teicoplanin is a critical antibiotic for treating Gram-positive infections in children.
- Current dosing guidelines lack sufficient pharmacokinetic data for pediatric populations.
- Suboptimal teicoplanin concentrations can lead to treatment failure and resistance.
Purpose of the Study:
- To determine the population pharmacokinetics (PK) of teicoplanin in pediatric patients.
- To evaluate the efficacy of current teicoplanin dosage regimens in children.
- To identify factors influencing teicoplanin PK variability in this age group.
Main Methods:
- A hospital-based pharmacokinetic study involving 39 pediatric patients up to 16 years of age.
- Serum samples were collected at multiple time points for analysis.
- A 2-compartment PK model incorporating weight-based linear scaling was developed and validated using Monte Carlo simulations.
Main Results:
- Teicoplanin population PK in children exhibits significant variability, with a wider area under the concentration-time curve (AUC) distribution compared to adults.
- Current dosing regimens resulted in suboptimal trough concentrations (<10 mg/liter) in a substantial percentage of patients by day 4.
- Weight significantly influenced teicoplanin clearance, with lower weight associated with higher relative drug exposure.
Conclusions:
- The pharmacokinetics of teicoplanin in children are highly variable and not adequately predicted by current dosing.
- A significant proportion of pediatric patients do not achieve target teicoplanin trough concentrations with standard regimens.
- Routine therapeutic drug monitoring is essential for optimizing teicoplanin dosing and ensuring treatment success in pediatric patients.
Abstract:
Teicoplanin is frequently administered to treat Gram-positive infections in pediatric patients. However, not enough is known about the pharmacokinetics (PK) of teicoplanin in children to justify the optimal dosing regimen. The aim of this study was to determine the population PK of teicoplanin in children and evaluate the current dosage regimens. A PK hospital-based study was conducted. Current dosage recommendations were used for children up to 16 years of age. Thirty-nine children were recruited. Serum samples were collected at the first dose interval (1, 3, 6, and 24 h) and at steady state. A standard 2-compartment PK model was developed, followed by structural models that incorporated weight. Weight was allowed to affect clearance (CL) using linear and allometric scaling terms. The linear model best accounted for the observed data and was subsequently chosen for Monte Carlo simulations. The PK parameter medians/means (standard deviation [SD]) were as follows: CL, [0.019/0.023 (0.01)] × weight liters/h/kg of body weight; volume, 2.282/4.138 liters (4.14 liters); first-order rate constant from the central to peripheral compartment (Kcp), 0.474/3.876 h(-1) (8.16 h(-1)); and first-order rate constant from peripheral to central compartment (Kpc), 0.292/3.994 h(-1) (8.93 h(-1)). The percentage of patients with a minimum concentration of drug in serum (Cmin) of <10 mg/liter was 53.85%. The median/mean (SD) total population area under the concentration-time curve (AUC) was 619/527.05 mg · h/liter (166.03 mg · h/liter). Based on Monte Carlo simulations, only 30.04% (median AUC, 507.04 mg · h/liter), 44.88% (494.1 mg · h/liter), and 60.54% (452.03 mg · h/liter) of patients weighing 50, 25, and 10 kg, respectively, attained trough concentrations of >10 mg/liter by day 4 of treatment. The teicoplanin population PK is highly variable in children, with a wider AUC distribution spread than for adults. Therapeutic drug monitoring should be a routine requirement to minimize suboptimal concentrations. (This trial has been registered in the European Clinical Trials Database Registry [EudraCT] under registration number 2012-005738-12.).
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