PHARMACOKINETICS IN THE CHILD

Pharmacokinetic studies have made many significant contributions to rational therapeutics in children. Pharmacokinetic data have helped distinguish between differences in drug disposition and drug sensitivity in children as compared to adults and led to the establishment of age-specific dosage guidelines. Factors influencing the observed differences between drug disposition in children and adults are reviewed. Specific examples utilizing anticancer drugs are presented. The use of model substrates to study hepatic drug metabolism and renal excretion in children is described and some results are discussed, The significance of genetic polymorphic drug metabolism is presented and the use of model substrates to determine individual metabolic phenotypes is described. The use of pharmacokinetic data to define the maximum-tolerated systemic exposure rather than the maximum-tolerated dosage oi anticancer drugs in children is presented.