KINPAK--a program for standardized pharmacokinetic analysis

Concept and routines of a new program package (KINPAK) for standardized evaluation of kinetic parameters are described. The package is mainly designed for the investigation of bioavailability or bioequivalence of pharmaceutical products. The data analysis is not based on compartmental or other specific model assumptions. Instead, the experimental data are fitted by new descriptive smoothing functions which are well adapted to the general form of concentration-time curves, but sufficiently flexible to give a good fit for nearly all experimental data sequences. The results are checked and, when necessary, corrected by a set of biologically based plausibility tests, which were heuristically derived from about 33,000 experimental concentrations. During the program development 2264 data sequences based on 40 different drugs were used as references; 95% could be evaluated successfully. The relevant biological parameters are calculated from the geometric properties of the fitted curves. Therefore, they will yield valid results even for curves which cannot be evaluated by compartmental models (e.g., multiple peak curves). The results are listed by KINPAK in various tables ready for presentation to regulatory agencies. Thus, errors of transcription are eliminated. The program, developed primarily for the investigation of bioavailability and bioequivalence in industrial drug research, should be of great interest for research laboratories, universities, and hospitals who are in need of a standardized evaluation system for comparative studies.