NEW DECISION SUPPORTS AND DATABASES FOR DRUG DOSAGE

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We propose to develop and implement new and improved software for better studies of the kinetic behavior of drugs in the body with new, more informative population pharmacokinetic and dynamic models of their behavior. These new models of individual drugs will also have new noise terms reflecting uncertainties in the therapeutic environment surrounding each patient's pharmacokinetic/dynamic model such as errors in preparation and administration of doses, errors in labelling times at which blood samples were obtained for serum level monitoring, and errors in measuring the serum concentrations of the drug and/or observed effects. The new models will thus have parameters which will serve as new databases for the quality of care (precision of therapy) each patient has received. When put together as population models, they will become indices of the quality of each center has given. The new software will be able to analyze the behavior of the great majority of drugs used in therapy today and in the future, free from corruption by the clinical environment. They will provide improved databases summarizing drug behavior and quality of therapy in patients. We also propose to develop and implement new controllers (dosage regimen designers) for decision support for drug dosage with these new models. They will now optimize the drug regimen with respect to rational performance criteria. We also propose to develop new larger population models, both linear and nonlinear, of drug behavior and effect, which can describe the additive, synergistic, or antagonistic effects of combined drug therapy on the hematopoetic system (the WBC, Hb, or platelet count), for example, and to develop new controllers for them as well. These resources are not available at present, though there is much activity in describing drug interactions and the combined effects of drugs. The proposed new models will permit, for the first time, truly quantitative, not just qualitative, descriptions of drug interactions. the new controllers for such models will permit adaptive control and decision support for drug therapy in the presence of these interactions, and optimal coordinated use of drug combinations to maximize benefits and minimize side effects such as those of drugs for AIDS and for cancer upon the hematopoetic system. Clinical studies will evaluate this work.