Population pharmacokinetics of high-dose methotrexate in children with acute lymphoblastic leukaemia.

Objective: To develop and a priori validate a methotrexate population pharmacokinetic model in children with acute lymphoblastic leukaemia (ALL), receiving high-dose methotrexate followed by folinic acid rescue, identifying the covariates that could explain part of the pharmacokinetic variability of methotrexate.

Methods: The study was carried out in 49 children (aged 6 months to 17 years) who received high-dose methotrexate (3 g/m(2) per course) in long-term treatment. In an index group (37 individuals; 1236 methotrexate plasma concentrations), a population pharmacokinetic model was developed using a nonlinear mixed-effects model.

Population pharmacokinetic analysis of vancomycin in patients with hematological malignancies.

This study determines vancomycin (VAN) population pharmacokinetics (PK) in adult patients with hematological malignancies. VAN serum concentration data (n = 1,004) from therapeutic drug monitoring were collected retrospectively from 215 patients. A one-compartment PK model was selected.

Population kinetics of tobramycin in neonates.

The population kinetics of tobramycin were studied in 140 neonates (100/40 patients for the index/validation groups, respectively) of 30 to 42 weeks' gestational age and 0.8 to 4.25 kg current body weight in their first 2 weeks of life, undergoing routine therapeutic drug monitoring of their tobramycin serum levels.

Valproate population pharmacokinetics in children.

Objective: A population analysis of the kinetics of valproic acid (VPA) in children with epilepsy was performed in order to characterize the covariates which influence VPA clearance (CL).

Methods: A total of 770 steady-state serum concentration samples was analysed. These were collected during VPA therapy from 255 children, aged 0.

Application of population pharmacokinetics to the optimization of theophylline therapy.

The aim of this study was to determine theophylline clearance (Cl) values in adult patients using serum concentrations gathered from routine clinical care. This information was used to estimate an a priori dosing regimen that would permit steady-state concentrations of 5-15 mg/litre, now recommended for the treatment of chronic asthma, and to evaluate the need to establish monitoring strategies when theophylline is given at these lower doses and when it can be expected that almost no adverse effects are likely. Retrospective data from 204 asthmatic and COPD patients, with a total of 517 serum concentrations, were studied.