CLINICAL PHARMACOKINETIC REGISTRATION FILE FOR NDA AND ANDA PROCEDURES

Pharmacokinetics is a relatively young branch of the life sciences, wh ich has developed rapidly in the last 15-20 years, thanks to a series of analytical achievements that have allowed drug concentrations to be measured in biological matrices with highly selective and sensitive m ethods. Most old drugs and all new drugs have been investigated in dep th to determine their absorption, distribution, metabolism and elimina tion. This has produced a huge body of data which have characterized d rugs through so-called fingerprint parameters. Today, pharmacokinetics plays a vital role throughout drug development from initial non-clini cal studies to clinical trials. In new drug development, simultaneous efforts in pharmacodynamic and pharmacokinetic studies have produced a high degree of synergy, the most useful expression of which is the id entification of a therapeutic window, where this can be achieved. Dose linearity/proportionality, gender effect, metabolism and possible pol ymorphism, studies on neonates/children and on elderly and diseased pa tients and the population approach, relative and absolute bioavailabil ity, possible interactions and the possible presence of a deep compart ment in the distribution are other important applications of pharmacok inetics. Major new developments in pharmaceutical technology which hav e produced controlled-release delivery systems and the market introduc tion of generics would never have occurred but for the active contribu tion of pharmacokinetics. This review is devoted to the investigations needed to prepare appropriate pharmacokinetic registration files for new drug applications (NDAs) and abbreviated or abridged new drug appl ications (ANDAs) required for generic drugs. Scientific literature, op erating guidelines and personal experience are the basis of this revie w, which describes a number of relevant examples in several specific a reas. (C) 1997 Italian Pharmacological Society.