[Pharmacokinetic studies in neonatology: regulatory and methodologic problems]

Pharmacokinetic studies in neonates are essential because of maturational changes in physiological functions during this period. International harmonization conferences have established guidelines for such studies, including recommendations on age ranges to be studied and description of methods and study design. Multiple blood sampling to obtain a full pharmacokinetic profile cannot be proposed in neonates. Population pharmacokinetic analysis, with minimal sampling schemes, is more appropriate but involves more subjects than the traditional approach. Population pharmacokinetic analysis also focuses on the influence of individual factors on pharmacokinetic parameters. Most studies performed with neonates have involved drugs with a narrow safety margin and cleared by renal or metabolic routes to study the impact of immaturity on drug concentrations and on clinical effects.