Optimal Sampling Theory: An Overview of Its Application to Pharmacokinetic Studies in Infants and Children

Abstract

Sick neonates, infants, and children often require drug therapy to ameliorate or cure disease. The success of drug therapy is directly dependent on administration of the optimal dose at the ideal dosing interval.1,,2 Determination of the optimal dose and dosing interval for a therapeutic agent requires a fundamental understanding of the complex interplay between a drug's pharmacokinetic and pharmacodynamic characteristics.1Unfortunately, pediatric practitioners often are confronted with the challenge of selecting a medication and defining a dose and dose interval without a clear understanding of the drug's pharmacokinetic and/or pharmacodynamic profiles or interactions. Our lack of understanding of these important, drug-specific pharmacologic characteristics places patients at tremendous risk for both suboptimal therapeutic results and serious untoward effects. Fortunately, over the past decade, we have witnessed great strides in our acceptance of performing pharmacokinetic studies in ill infants and children and the application of these data to the design of age-specific dosing regimens.3,,4 Nevertheless, unique challenges and limitations remain that complicate the performance of detailed, critical pharmacokinetic assessments of drugs in sick infants and children. The purpose of this article is to address some of the more important variables that influence the design and successful execution of pharmacokinetic evaluations in pediatric patients. The determination of a drug's pharmacokinetic profile involves a detailed, critical assessment of the processes of absorption, distribution, metabolism, and excretion. As noted above, a fundamental knowledge of each of these processes is required for the design of an optimal dosing regimen for the treatment of specific disorders. Each of these processes must be integrated with patient-specific factors that influence directly a drug's disposition in the body. The more important clinical variables that influence a drug's disposition in the body are shown in Table 1. Of the variables outlined in Table …