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Published on: September 18, 2013
Population pharmacokinetics and dosing optimization of teicoplanin in children with malignant haematological disease
Wei Zhao1,2,3,4, Daolun Zhang3, Thomas Storme5
1Sino-French Pediatric Research Center, Department of Clinical Pharmacy, School of Pharmaceutical Sciences, Shandong University, Jinan.
Insights
Optimizing teicoplanin dosing in children with hematological malignancy is crucial. This study developed a population pharmacokinetic model to individualize therapy, improving drug efficacy and reducing sub-therapeutic levels in this high-risk group.
Area of Science:
- Pharmacology
- Pediatric Oncology
- Infectious Diseases
Background:
- Children with hematological malignancy have unique pharmacokinetic parameters.
- Inadequate antibacterial therapy increases morbidity and mortality in this population.
- Limited pediatric data necessitates optimized dosing regimens for drugs like teicoplanin.
Purpose of the Study:
- To evaluate the population pharmacokinetics of teicoplanin in children with hematological malignancy.
- To define an appropriate and individualized teicoplanin dosing regimen for this high-risk group.
- To improve therapeutic drug monitoring and outcomes.
Main Methods:
- Population pharmacokinetics of teicoplanin were analyzed using non-mem software in 85 children.
- Covariate analysis identified bodyweight and creatinine clearance as significant factors influencing teicoplanin clearance.
- A two-compartment pharmacokinetic model with first-order elimination was developed and validated.
Main Results:
- 48% of children on the current dose (10 mg/kg/day) had sub-therapeutic trough concentrations.
- Recommended doses to reach target AUC varied by age: 18 mg/kg for infants, 14 mg/kg for children, and 12 mg/kg for adolescents.
- Patient-tailored dosing reduced variability in AUC and Css,min compared to weight-based dosing.
Conclusions:
- This study provides the first population pharmacokinetic data for teicoplanin in pediatric hematological malignancy.
- Evidence-based support for individualizing teicoplanin therapy in this vulnerable population was established.
- Optimized dosing regimens are essential for improving treatment outcomes.
Aim:
Children with haematological malignancy represent an identified subgroup of the paediatric population with specific pharmacokinetic parameters. In these patients, inadequate empirical antibacterial therapy may result in infection-related morbidity and increased mortality, making optimization of the dosing regimen essential. As paediatric data are limited, our aim was to evaluate the population pharmacokinetics of teicoplanin in order to define the appropriate dosing regimen in this high risk population.
Methods:
The current dose of teicoplanin was evaluated in children with haematological malignancy. Population pharmacokinetics of teicoplanin were analyzed using nonmem software. The dosing regimen was optimized based on the final model.
Results:
Eighty-five children (age range 0.5 to 16.9 years) were included. Therapeutic drug monitoring and opportunistic samples (n = 143) were available for analysis. With the current recommended dose of 10 mg kg(-1) day(-1) , 41 children (48%) had sub-therapeutic steady-state trough concentrations (Css,min <10 mg l(-1) ). A two compartment pharmacokinetic model with first order elimination was developed. Systematic covariate analysis identified that bodyweight (size) and creatinine clearance significantly influenced teicoplanin clearance. The model was validated internally. Its predictive performance was further confirmed in an external validation. In order to reach the target AUC of 750 mg l(-1) h 18 mg kg(-1) was required for infants, 14 mg kg(-1) for children and 12 mg kg(-1) for adolescents. A patient-tailored dose regimen was further developed and reduced variability in AUC and Css,min values compared with the mg kg(-1) basis dose, making the modelling approach an important tool for dosing individualization.
Conclusions:
This first population pharmacokinetic study of teicoplanin in children with haematological malignancy provided evidence-based support to individualize teicoplanin therapy in this vulnerable population.
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