Ramos-Martín, VPaulus, SSiner, SScott, EPadmore, KNewland, PDrew, R JFelton, T WDocobo-Pérez, FPizer, BPea, FPeak, MTurner, M ABeresford, M WHope, W W2015-11-272015-11-272014-11Ramos-Martín V, Paulus S, Siner S, Scott E, Padmore K, Newland P, et al. Population pharmacokinetics of teicoplanin in children. Antimicrob. Agents Chemother. 2014; 58(11):6920-70066-4804http://hdl.handle.net/10668/2082Clinical Trial; Journal Article; Research Support, Non-U.S. Gov't. This trial has been registered in the European Clinical Trials Database Registry [EudraCT] under registration number 2012-005738-12.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.).enStaphylococcus aureus resistente a meticilinaMétodo de MontecarloPruebas de sensibilidad MicrobianaInfecciones estafilocócicasTeicoplaninaMedical Subject Headings::Named Groups::Persons::Age Groups::AdultMedical Subject Headings::Chemicals and Drugs::Chemical Actions and Uses::Pharmacologic Actions::Therapeutic Uses::Anti-Infective Agents::Anti-Bacterial AgentsMedical Subject Headings::Named Groups::Persons::Age Groups::ChildMedical Subject Headings::Named Groups::Persons::Age Groups::Child::Child, PreschoolMedical Subject Headings::Chemicals and Drugs::Heterocyclic Compounds::Heterocyclic Compounds, 1-Ring::Azoles::Imidazoles::CreatinineMedical Subject Headings::Check Tags::FemaleMedical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::HumansMedical Subject Headings::Named Groups::Persons::Age Groups::InfantMedical Subject Headings::Check Tags::MaleMedical Subject Headings::Organisms::Bacteria::Endospore-Forming Bacteria::Gram-Positive Endospore-Forming Bacteria::Gram-Positive Endospore-Forming Rods::Staphylococcaceae::Staphylococcus::Staphylococcus aureus::Methicillin-Resistant Staphylococcus aureusMedical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Diagnosis::Diagnostic Techniques and Procedures::Clinical Laboratory Techniques::Microbiological Techniques::Microbial Sensitivity TestsMedical Subject Headings::Information Science::Information Science::Systems Analysis::Operations Research::Monte Carlo MethodMedical Subject Headings::Diseases::Bacterial Infections and Mycoses::Bacterial Infections::Gram-Positive Bacterial Infections::Staphylococcal InfectionsMedical Subject Headings::Chemicals and Drugs::Carbohydrates::Glycoconjugates::Glycopeptides::TeicoplaninMedical Subject Headings::Named Groups::Persons::Age Groups::Adolescentresearch article25224001open access10.1128/AAC.03685-141098-6596PMC4249354