Pharmacokinetics of teicoplanin in pediatric patients

Terragna, A; Ferrea, G.; Loy, Anna; Danese, Antonio; Bernareggi, A.; Cavenaghi, L; Rosina, R.

doi:10.1128/aac.32.8.1223

Cited by 26 publications

(14 citation statements)

References 15 publications

(25 reference statements)

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“…Great variation for PK parameters of teicoplanin was presented in children. The typical population values of CL in our study (0.014 L/h/kg) was similar to the range of 0.015-0.024 L/h/kg reported in non-PICU Caucasians previously, but lower than that in PICU Caucasians (0.03-0.074 L/h/kg) (Aarons et al, 1998;Lukas et al, 2004;Ramos-Martin et al, 2014;Reed et al, 1997;Sanchez et al, 1999;Terragna et al, 1988;Zhao et al, 2015). Due to widespread systemic inflammation, patients may often have an ARC in PICU patients (Van Der Heggen et al, 2019), and increased volume of distribution and drug clearance has been observed for hydrophilic drugs, resulting in sub-therapeutic trough concentrations (Hirai et al, 2016).…”

Section: Discussionsupporting

confidence: 90%

Population Pharmacokinetics and Model-Based Dosing Optimization of Teicoplanin in Pediatric Patients

et al. 2020

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Objectives: The pharmacokinetics (PK) of teicoplanin differs in children compared with adults. Our aim was to determine the PK of teicoplanin in an Asian pediatric population and to optimize dosage regimens.Methods: This was a retrospective PK study and all the data were collected from hospitalized children. We developed a population PK model using sparse data, and Monte Carlo simulation was used to assess the ability of standard teicoplanin regimen and other different dosage regimens. The optimal dosing regimens were defined as achieving the target trough concentration (Cmin) of 10 mg/L and pharmacokinetic/pharmacodynamic (PK/PD, [AUC24/MIC]) of 125 for moderate infection. For severe infection, the optimal dosing regimens were defined as achieving the target 15 mg/L and AUC24/MIC of 345.Results: 159 children were included and 1.5 samples/children on average were provided. Estimated clearance of teicoplanin was 0.694 L/h (0.784/L/h/70 kg) and volume of distribution was 1.39 L. Teicoplanin standard loading dose was adequate for moderate infection, while 13 mg/kg was needed for severer infection. With standard maintenance doses, both patients with moderate and severe infection failed to achieve the target Cmin. 12 and 16 mg/kg/day were required to achieve a Cmin ≥ 10 and 15 mg/L, respectively. However, standard maintenance dose was adequate to achieve AUC24/MIC ≥ 125 for moderate infection, and 12 mg/kg/day was needed to achieve AUC24/MIC ≥ 345 for severe infection. Lower weight and serum creatinine were associated with higher dose.Conclusion: Optimal doses based on the target Cmin were higher than that based on the PK/PD target. To achieve the Cmin and PK/PD targets simultaneously, a standard loading dose was adequate for moderate infection based on simulation, while dosing higher than standard doses were required in other situation. Further clinical studies with rich sampling from children is required to confirm our findings.

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Section: Discussionsupporting

confidence: 90%

Population Pharmacokinetics and Model-Based Dosing Optimization of Teicoplanin in Pediatric Patients

et al. 2020

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“…The clinical utility of the opportunistic sampling design is undoubtedly in paediatric pharmacokinetic studies. In the present study, the median estimated volume of distribution at steady‐state was 1.1 l kg –1 , which was consistent with previous pharmacokinetic studies of teicoplanin in children using rich pharmacokinetic sampling design and non‐compartment pharmacokinetic analysis .…”

Section: Discussionmentioning

confidence: 99%

“…It is mainly bound to albumin (90%) and eliminated predominantly by the kidney . Some pharmacokinetic studies of teicoplanin have been conducted in children , however, only in children without HM. As demonstrated in our previous pharmacokinetic study of vancomycin, eight children with HM represent an identified sub‐population of patients with proper pharmacokinetic parameters, different from other paediatric patients.…”

Section: Introductionmentioning

confidence: 99%

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

Zhao

Zhang

Storme

et al. 2015

Brit J Clinical Pharma

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AIMChildren 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. METHODSThe 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. RESULTSEighty-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 (C ss,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 C ss,min values compared with the mg kg -1 basis dose, making the modelling approach an important tool for dosing individualization. WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT• The pharmacokinetics of teicoplanin show large inter-individual variability, making therapeutic drug monitoring useful to optimize an individual dose, especially in children.• Children with malignant haematological disease are a special group of patients with proper pharmacokinetic parameters, different from other paediatric patients. The pharmacokinetic data of teicoplanin are missing in this vulnerable population, thereby leading to the empirical therapy in clinical practice. WHAT THIS STUDY ADDS• With the current recommended dose of 10 mg kg À1 day À1 , 48% of patients had sub-therapeutic steady-state trough concentrations (C ss,min <10 mg l À1 ). The dose needs to be increased.• A population pharmacokinetic analysis has been conducted in 85 children. Body weight and creatinine clearance have been identified as significant covariates influencing teicoplanin clearance. CONCLUSIONSThis 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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“…A three-compartment model was selected to describe teicoplanin disposition [18]. The terminal half life of teicoplanin in children being 57.9 h (SE 4.16) [22], and in order to obtain as much information as possible, we derived the pharmacokinetic parameters by fitting the whole medication history of each patient. Unfortunately, some babies apparently did not receive the prescribed dose, despite the fact that the drug administration procedure was carefully explained to the nurses.…”

Section: Discussionmentioning

confidence: 99%

Use of Teicoplanin in Preterm Neonates with Staphylococcal Late-Onset Neonatal Sepsis

Degraeuwe¹,

Beuman²,

Tiel

et al. 1998

Neonatology

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Objective: To study the clinical pharmacology of teicoplanin in babies admitted to a newborn intensive care unit, by monitoring serum levels, efficacy and potential side effects. Methods: An open, nonrandomized descriptive study was performed in the neonatal intensive and high care unit of the Universtiy Hospital Maastricht, The Neterlands. Twenty-three preterm neonates, gestational age ranging from 26 to 32 weeks (median 28.4 weeks), postnatal age from 5 to 47 days, and birth weight from 570 to 1,740 g, presenting with (suspected) late onset septicemia, were studied. Of 21 culture-proven septicemias, 20 were caused by staphylococci. The teicoplanin loading dose was 15 mg/kg i.v., followed by a maintenance dose of 8 mg/kg every 24 h. Intravenous gentamicin was also administered pending blood culture. Serum teicoplanin concentrations were measured by fluorescence polarization immunoassay. Clinical and microbiological cure/failure rates were determined and possible side effects were monitored. Results: The study of individual pharmacokinetics during multiple-dose intravenous infusions was rendered impossible by apparently inaccurate dosing. Peak (30 min after end of the infusion) and trough teicoplanin levels were stable throughout the study and averaged 27.8 (interquartile range 23.7–32.9) and 12.3 (interquartile range 9.1–16.8) mg/l, respectively. The microbiological and clinical cure rates were 90% in gram-positive septicemia. There was no apparent toxicity. Conclusions: Inaccurate drug administration was a problem in this study, making a multidose pharmacokinetic study impossible. It is possible that inaccurate drug administration and not current dosage guidelines yielded trough levels below 10 mg/l in 57 (32%) of 176 instances. This pharmaceutical aspect clearly warrants further study. However, microbiological and clinical cure rates were high in gram-positive septicemias. No side effects attributable to teicoplanin therapy were encountered.

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Pharmacokinetics of teicoplanin in pediatric patients

Cited by 26 publications

References 15 publications

Population Pharmacokinetics and Model-Based Dosing Optimization of Teicoplanin in Pediatric Patients

Population Pharmacokinetics and Model-Based Dosing Optimization of Teicoplanin in Pediatric Patients

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

Use of Teicoplanin in Preterm Neonates with Staphylococcal Late-Onset Neonatal Sepsis

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