title: 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. 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.).
authors.affiliation: Department 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.
authors.forename: V
authors.initials: V
authors.lastname: Ramos-Martín
authors.affiliation: Alder Hey Children's NHS Foundation Trust, Liverpool, United Kingdom.
authors.forename: S
authors.initials: S
authors.lastname: Paulus
authors.affiliation: Alder Hey Children's NHS Foundation Trust, Liverpool, United Kingdom.
authors.forename: S
authors.initials: S
authors.lastname: Siner
authors.affiliation: Alder Hey Children's NHS Foundation Trust, Liverpool, United Kingdom.
authors.forename: E
authors.initials: E
authors.lastname: Scott
authors.affiliation: Alder Hey Children's NHS Foundation Trust, Liverpool, United Kingdom.
authors.forename: K
authors.initials: K
authors.lastname: Padmore
authors.affiliation: Alder Hey Children's NHS Foundation Trust, Liverpool, United Kingdom.
authors.forename: P
authors.initials: P
authors.lastname: Newland
authors.affiliation: Alder Hey Children's NHS Foundation Trust, Liverpool, United Kingdom.
authors.forename: R J
authors.initials: RJ
authors.lastname: Drew
authors.affiliation: Manchester Academic Health Science Centre, NIHR Translational Research Facility in Respiratory Medicine, University Hospital of South Manchester NHS Foundation Trust, Manchester, United Kingdom.
authors.forename: T W
authors.initials: TW
authors.lastname: Felton
authors.affiliation: Unidad Clínica de Enfermedades Infecciosas y Microbiología, Hospital Universitario Virgen Macarena, Seville, Spain.
authors.forename: F
authors.initials: F
authors.lastname: Docobo-Pérez
authors.affiliation: Department of Women's and Children's Health, Institute of Translational Medicine, University of Liverpool, Liverpool, United Kingdom Alder Hey Children's NHS Foundation Trust, Liverpool, United Kingdom.
authors.forename: B
authors.initials: B
authors.lastname: Pizer
authors.affiliation: Institute of Clinical Pharmacology, Azienda Ospedaliero-Universitaria Santa Maria della Misericordia, Udine, Italy Department of Experimental and Clinical Medical Sciences, University of Udine, Udine, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Pea
authors.affiliation: Alder Hey Children's NHS Foundation Trust, Liverpool, United Kingdom.
authors.forename: M
authors.initials: M
authors.lastname: Peak
authors.affiliation: Department of Women's and Children's Health, Institute of Translational Medicine, University of Liverpool, Liverpool, United Kingdom Liverpool Women's NHS Foundation Trust, Liverpool, United Kingdom.
authors.forename: M A
authors.initials: MA
authors.lastname: Turner
authors.affiliation: Department of Women's and Children's Health, Institute of Translational Medicine, University of Liverpool, Liverpool, United Kingdom Alder Hey Children's NHS Foundation Trust, Liverpool, United Kingdom.
authors.forename: M W
authors.initials: MW
authors.lastname: Beresford
authors.affiliation: Department 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 william.hope@liverpool.ac.uk.
authors.forename: W W
authors.initials: WW
authors.lastname: Hope
mesh_terms: D000293:Adolescent; D000328:Adult; D000900:Anti-Bacterial Agents / Q000097:blood / Q000493:pharmacokinetics*; D002648:Child; D002675:Child, Preschool; D003404:Creatinine / Q000097:blood; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects*; D008826:Microbial Sensitivity Tests; D009010:Monte Carlo Method; D013203:Staphylococcal Infections / Q000188:drug therapy / Q000382:microbiology; D017334:Teicoplanin / Q000097:blood / Q000493:pharmacokinetics*
chemical_list: D000900:Anti-Bacterial Agents; D017334:Teicoplanin; D003404:Creatinine