Guidelines on paediatric dosing on the basis of developmental physiology and pharmacokinetic considerations

The approach to paediatric drug dosing needs to be based on the physiological characteristics of the child and the pharmacokinetic parameters of the drug. This review summarises the current knowledge on developmental changes in absorption, distribution, metabolism and excretion and combines this knowledge with in vivo and in vitro pharmacokinetic data that are currently available. In addition, dosage adjustments based on practical problems, such as child-friendly formulations and feeding regimens, disease state, genetic make-up and environmental influences are presented. Modification of a dosage based on absorption, depends on the route of absorption, the physico chemical properties of the drug and the age of the child. For oral drug absorption, a distinction should be made between the very young and children over a few weeks old. In the latter case, it is likely that practical considerations, like appropriate formulations, have much greater relevance to oral drug absorption. The volume of distribution (V(d)) may be altered in children. Hydrophilic drugs with a high V(d) in adults should be normalised to bodyweight in young children (age