POPULATION PHARMACOKINETICS IN VETERINARY-MEDICINE - POTENTIAL USE FOR THERAPEUTIC DRUG-MONITORING AND PREDICTION OF TISSUE RESIDUES

Population pharmacokinetics can be defined as a study of the basic fea tures of drug disposition in a population accounting for the influence of diverse pathophysiological factors on pharmacokinetics, and explic itly estimating the magnitude of the interindividual and intraindividu al variability. It is used to identify subpopulations of individuals t hat may present with differences in drug kinetics or in kinetic/dynami c responses. Rooted in procedures used in engineering systems, populat ion pharmacokinetics methods were conceived as a means to determine th e pharmacokinetic profile in populations in which a sparse number of s amples were obtained per individual, such as those in late stage human clinical trials. This is the situation commonly encountered in all as pects of veterinary medicine. The exploratory nature of this technique allows one to probe relationships between clinical factors (such as a ge, gender, renal function, etc.) and drug disposition and/or effect. Similarly, the utilization of these techniques in the clinical researc h phases of drug development optimize the determination of efficacy an d safety of drugs. Given the observational nature of most studies publ ished so far, statistical methods to validate the population models ar e necessary. Simulation studies may be conducted to explore data colle ction designs that maximize information yield with a minimum expenditu re of resources. The breadth of this approach has allowed population s tudies to be more commonly employed in all areas of drug therapy and c linical research. Finally, in veterinary medicine, there is an additio nal field in which population studies are potentially ideally suited: the application of this methodology to the study of tissue drug deplet ion and drug residues in production animals, and the establishment of withdrawal times tailored to the clinical or production conditions of populations or individuals. Such application would provide a major ste p toward assuring a safe food supply under a wide variety of dose and off-label clinical uses. Population pharmacokinetics is an ideal metho d for generating data in support of the implementation of flexible lab elling policies and extralabel drug use recently approved under AMDUCA (Animal Medicinal Drug Use Clarification Act. 21 CFR Part 530).