Population Pharmacokinetics of Teicoplanin in Children

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. 2). A significant rise in infections caused by methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-resistant coagulasenegative staphylococci (CoNS) has led to increased use of glycopeptides in the last decade (3, 4). Both vancomycin and teicoplanin are used for treatment of invasive infections caused by Gram-positive organisms, especially those that are resistant to ␤-lactam antibiotics (5, 6). The currently recommended regimen for teicoplanin in adults is 3 loading doses of 400 mg every 12 hours followed by a maintenance dose of 400 mg/day. In contrast, children receive 3 loading doses of 10 mg/kg of body weight every 12 hours followed by a maintenance dose of 10 mg/kg daily (7). However, there is a relative paucity of information to justify these regimens in children and even less information to identify optimal dosing strategies.Regulatory authorities such as the European Medicines Agency (EMA) have developed strategies to facilitate the safe and effective use of medicines in neonates and children (8). EMA supports the extrapolation of information from adults to children provided there are adequate safety data in the latter and the pharmacodynamics can reasonably assumed to be the same in both populations. This approach requires the development of robust population pharmacokinetic (PK) models in both adults and children, which facilitates the design of regimens that enable drug exposures in both populations to be matched (8).Teicoplanin is largely used without routinely measuring concentrations in the majority of pediatric patients. In our pediatric hospital setting, we have observed anecdotal cases of clinical failures with teicoplanin therapy and have observed "MIC creep" for CoNS with MICs at the breakpoint (4 mg/ liter) (unpublished data). To further investigate the clinical pharmacology of teicoplanin and to provide an insight into effective regimens for children, we performed a population PK study. The specific objectives of this study were to (i) describe the population PK of teicoplanin in children in a hospital setting, (ii) explore the percentage of patients attaining a predose minimum concentration (C min ) of Ͼ10 mg/liter, (iii) define the area under the concentration-time curve (AUC) distributions follo...

Population pharmacokinetics and dosing optimization of teicoplanin in children with malignant haematological disease

“…All these three studies in adults have shown that the population pharmacokinetics of teicoplanin were well described by a two compartment model and the elimination of teicoplainin was significantly influenced by renal function. Our findings are also in agreement with those of a pharmacokinetic study in critically ill children, showing that 54% of patients had C ss,min <10 mg l –1 with the current dose regimen . There are very limited data in neonates.…”

Population pharmacokinetics and pharmacodynamics of teicoplanin in neonates: making better use of C-reactive protein to deliver individualized therapy

“…This comparison was based on Monte Carlo simulations conducted on a previous teicoplanin PK study with older children and adults. 6 Exposure -response relationships A newly described PD index (AUC:EC 50 ) was used to link drug exposure with therapeutic response (terminal CRP concentration). 21 An E max sigmoidal model was fitted to the data.…”

“…4,5 In older children, there is considerable pharmacokinetic (PK) variability in comparison with adults, with a much wider drug exposure (AUC) distribution among children. 6 Little is known about the pharmacokinetics (PK) of teicoplanin in neonates.…”

P027 Teicoplanin: evaluation of serum concentrations

“…[1][2][3] The summary of the research available showed that patients are not achieving target concentrations. This retrospective audit aimed to evaluate whether patients were achieving target serum concentrations.…”