Populationspharmakokinetik von Indomethacin bei Kindern mit Salzverlusttubulopathien

The objective of our study was to develop a population pharmacokinetic model to assess the influence of subject covariates on the pharmacokinetics of indomethacin in children. Data were collected from 38 patients (age 3 months - 20 years) suffering from salt-losing tubulopathy. Infants received a dosis of indomethacin of 2 mg/kg at an average. Population analysis of the 211 plasma concentrations obtained was conducted using NONMEM. The concentration-time course of indomethacin was best described by a one-compartment model with first order absorption, ka fixed to previously reported value. The most significant covariate effect was body surface area (BSA) and so integrated in the final model. The population means for clearance (CL) and volume of distribution (V) were 2,67 l/m²/h and 23,6 l/m². Interindividual variability in CL and V was 42% and 36%. Intraindividual variability (residual error) was 69%. The population estimates can be used to determine typical values of CL and V allowing the prediction of individualized doses of indomethacin. Although the pharmacokinetic estimates will be affected by both interindividual and intraindividual variation, it is anticipated that this approach will optimize treatment, especially when dealing with the use of off-lable drugs in children and infants.