Population pharmacokinetic analysis during the first 2 years of life: an overview

Abstract

Three decades after its introduction, pharmacokinetic population approaches have become a reference method for drug modelling, particularly in paediatrics. The main practical limitation in this specific population is the collected blood volume. Pharmacokinetic population approaches using sparse sampling may resolve this issue. The pharmacokinetics of many drugs have been studied during the last 25 years using such methods. This review summarizes all of the published studies concerning population pharmacokinetic approaches in paediatric subjects from neonate to 2 years old. A literature search was conducted using the PubMed database, from 1985 to December 2010, using the following terms: pharmacokinetic(s), population, paediatric/pediatric and neonate(s). Articles were excluded if they were not pertinent according to our criteria. References of all relevant articles were also evaluated. Ninety-eight studies were included in this review. The following information was extracted from the articles: drug name, therapeutic class, population size, age of patients, number of samples per patient, covariates used for clearance and volume of distribution estimates, software used for modelling and validation methods. An increasing rate of publications over the years was observed; 44 different drugs were studied using a pharmacokinetic population approach. Antibacterials were the most studied class of drugs, including a large number of studies devoted to vancomycin and gentamicin. It must be underlined that few studies have been performed on anticonvulsant drugs and anaesthetics used in clinical daily practice conditions.