PHARMACOKINETIC MODELS FOR SCALE-UP TO HUMANS

THE LONG-TERM OBJECTIVES OF THIS PROJECT ARE TO DEVELOP AND MARKET PERSONAL COMPUTER-BASED SOFTWARE FOR PROVIDING PHARMACOKINETIC GUIDANCE TO THE DEVELOPMENT AND USE OF DRUGS WITH NARROW THERAPEUTIC INDICES, WHETHER THEY ARE USED ALONE, IN COMBINATION OR INPHASE I CLINICAL TRIALS. EMPHASIS WILL BE PLACED ON SUSCEPTIBLE POPULATIONS INCLUDING CHILDREN AND THE ELDERLY. FOR THIS PARTICULAR PHASE I PROJECT, THE SPECIFIC AIM IS TO DEVELOP MODELS THAT WILL PREDICT THE PHARMACOKINETIC BEHAVIOR OF CANCER CHEMOTHERAPY AGENTS IN HUMANS ON THE BASIS OF DATA OBTAINED IN EXPERIMENTAL ANIMALS. MODELS WILL BE DEVELOPED BY MULTIPLE REGRESSION ANALYSIS OF PRECLINICAL AND CLINICAL DATA FOR 6 DRUGS WITH DIFFERING METABOLIC FATES, AND VALIDATED BY TESTING AGAINST OTHER AGENTS. THE PRODUCT WILL CONSIST OF INTERACTIVE PROGRAMS WHICH WILL BE AVAILABLE EVENTUALLY ON FLOPPY DISKETTES. THE SAVINGS IN COST AND TIME WITH RESPECT TO DRUG DEVELOPMENT AS A RESULT OF THIS PHASE I ACTIVITY, AND THE BENEFITS IN SAFETY, REDUCED MEDICAL COSTS INCURRED IN TREATING ADVERSE DRUG EFFECTS, AND POTENTIAL FOR DEVELOPING INDIVIDUALIZED THERAPY IN THE LONG-TERM, PRESENT SIGNIFICANT COMMERCIAL POSSIBILITIES.