The objectives of the proposed program are to carry out clinical pharmacokinetic and biopharmaceutic studies to increase the safety and efficacy of drug therapy in man. Clinical Pharmacokinetics Laboratories at two major hospitals under the direction of qualified clinical pharmacokineticists-supported by a panel of specialists in pharmacokinetics and drug analysis--will develop individualized dosage regimens for such drugs as digoxin, diphenylhydantoin, quinidine, theophylline and gentamycin based on physiologic and pharmacokinetic parameters, and will explore pharmacokinetic aspects of unusual drug responses and special problems such as drug dosage regimens for patients undergoing hemodialysis. These regimens will be refined and adjusted on the basis of regular monitoring of plasma concentrations and (where feasible) response. The clinical research will be interdigitated with a comprehensive program focusing on basic pharmacokinetics research on drug bioavailability, time course of reversible pharmacologic effects and development of physiologically realistic biomathematical models.