Therapeutic drug monitoring in the neonate and paediatric age group. Problems and clinical pharmacokinetic implications

Abstract

Therapeutic drug monitoring should encompass not only serum concentration monitoring but also assessments of organ and clinical functions. This is especially important in children, in whom receptor drug concentration or sensitivity may be different from that seen in the adult population. Therapeutic end-points should be identified and serum drug concentrations adjusted to meet these goals. This is further complicated by the added impact of pharmacokinetic idiosyncrasies displayed by children, coupled with the routine pitfalls of therapeutic drug monitoring seen in any patient population. Neonates and infants present the additional challenge of having a set of mechanisms whose degree of maturation sometimes changes on a day-to-day basis with alarming rapidity. It is this phenomenon which makes the definition of pharmacokinetic parameters following a single dose so unreliable and potentially hazardous. Therapy should be based not only on the capacity of the infant to eliminate and respond to a particular agent, but also on the understanding of the dynamic changes that will occur on an ongoing maturational basis. A basic familiarity with the patient population under study is essential in obtaining relevant data for pharmacokinetic analysis. Special consideration in children should focus on potential problems with drug administration, drug absorption, metabolite patterns, changing drug disposition, idiosyncratic reactions, receptor sensitivity and chronopharmacokinetics. As with other patient populations, serum drug concentration monitoring is only a small part of the clinical scenario, the whole of which must be the basis for therapeutic decisions and pharmacodynamic titration.