ADAPTIVE-CONTROL OF DRUG-DOSAGE REGIMENS - BASIC FOUNDATIONS, RELEVANT ISSUES, AND CLINICAL EXAMPLES

In this paper we examine several of the fundamental foundations and re levant clinical issues in adaptive control of drug dosage regimens for patients. Truly individualized therapy with drugs having narrow margi ns of safety first requires a practical pharmacokinetic/dynamic model of the behavior of a drug, Past experience with a drug is stored in th e form of a population model. Next, using the information in such a mo del and its relationship to the incidence of adverse reactions, a spec ific, explicit therapeutic goal must be selected by the responsible cl inician, based on the patient's need for the drug and the risk of adve rse reactions felt to be justified by each patient's need, small, mode rate, or great. Individualized drug therapy thus begins with the selec tion of individualized therapeutic goals (low, moderate, or high) for each patient. Using subsequent feedback from the patient's serum drug levels, and using Bayesian fitting, the model is then linked to each p atient as a patient-specific model. Control of the model by the dosage regimen increasingly controls the patient, to better obtain the desir ed explicit therapeutic goals. This process is essentially similar to that of a flight control or missile guidance system.