IMPLEMENTATION OF AN EFFECTIVE PHARMACOKINETICS RESEARCH PROGRAM IN INDUSTRY

Over the past decade the application of pharmacokinetic data in drug development has gradually increased. Today it is well recognized that successful drug development programs include meaningful supportive pharmacokinetic data. An effective pharmacokinetic program begins at the preclinical phase with well defined objectives to support pharmacology/toxicology programs, to determine effective/toxic blood concentration ranges and to help in expediting early phase I studies in man. The clinical pharmacokinetic program may be classified as follows: i) pharmacokinetics during safety and tolerance studies in man to determine key pharmacokinetic parameters including linearity over the utilized dose range, and related effective and toxic blood concentrations; ii) pivotal pharmacokinetic studies to determine metabolism profile and major active/inactive metabolite(s) in man, extent of first-pass metabolism, absolute and/or relative bioavailability, effect of food on absorption, dose proportionality, route and mechanism of elimination, bioequivalency of final dosage forms and to establish therapeutic dosing regimens; and iii) studies supporting labeling to determine pharmacokinetics in special populations, effect of disease states and interactions with concomitantly administered drugs. A successful pharmacokinetic program is done prospectively to support the design of safety evaluation studies, to assist in expediting the Phase I/II programs, and to facilitate the Phase III trials in patients.