Drug use in the neonate: interrelationships of pharmacokinetics, toxicity, and biochemical maturity

With advances in technology, increasing numbers of premature and very ill neonates are surviving and being referred for treatment to neonatal intensive-care units. A major feature of the treatment they receive is therapy with drugs. However, because of relatively limited information available in the area of neonatal pharmacokinetics, the few drugs that currently can be monitored directly, and the lack of an effective mechanism for measuring the biochemical and functional maturity of the neonate, especially as it relates to drug clearance, therapy of neonates with drugs is certainly more hazardous and possibly less effective than in adult patients. Toxic reactions of neonates to drug therapy can usually be related to the unique pharmacokinetic processes seen in this group, particularly to the maturity of clearance mechanisms. This is the basis for a link between maturity and drug efficacy or toxicity. In this usage, maturity refers to the functional capacity of organs and biochemical pathways. Of particular concern in this regard is kidney function and the activity of drug-metabolizing enzyme systems. Because direct assessment of these functions in the neonate is difficult, other types of maturity markers that can be easily measured and which relate to drug clearance need to be identified. Such markers could serve as a guide to the physician who is planning drug therapy for a neonatal patient. Several studies looking for a gestational age marker have provided some indication that biochemical maturity markers do exist and simply await discovery, thus affording an integration of pharmacokinetics and pathophysiology to achieve a more rational and effective therapeutic approach.