Pharmacokinetic analyses with RUGFIT: an interactive pharmacokinetic computer program.

Abstract

RUGFIT is an interactive computer program to fit polyexponential equations to experimental points without the need of assumptions about the number of exponential terms and without the need of initial parameter estimates. The fitting is performed by iterative stripping minimizing the sum of squared residuals. This procedure leads to multiple model equations describing the profile of the y-value in time, that are compared with the test of Boxenbaum et al. The examples analysed in this paper are: a plasma decay curve after an intravenous bolus injection and one after an oral gift, a dA/dt versus time curve with a lag time and a curve possibly reflecting an entero-hepatic recirculation. The outcomes are, where possible, compared with the outcomes obtained with the computer programs CFT3, NONLIN, and NONLINEAR (SPSS). The latter three programs sometimes run into a local minimum, as the outcomes obtained with RUGFIT were close to the best ones obtained with the other programs. The analyses with RUGFIT show that a choice of an inadequate model equation can lead to a marked error in the value of the area under the curve that may result in a marked error of, for instance, the bioavailability. The procedures of RUGFIT are illustrated in the Appendix. RUGFIT also contains options to calculate microparameters, to simulate dosage regimes, to calculate exponents and intercepts from rate constants and to analyse time effect relationships.