USE OF SIMULTANEOUS COMPUTER FITTING TO ESTIMATE THE APPARENT ABSORPTION RATE-CONSTANT

In this study we explored an alternative approach to specifically determine the apparent absorption rate constant (ka) and the initial disposition macro-rate constant (.alpha.) without intravenous dose data. Data sets were simulated with ka values in a range of .+-. 70% of .alpha.. A 10%, uniformly distributed, random error was added to all the simulation parameters and to the concentration values. The data sets were fit individually (one data set) and simultaneously (all possible combinations of two, four, or six data sets) using NONLIN. The parameters .alpha., .beta. (the terminal disposition rate constant), and k21 (the exit rate constant from the peripheral compartment) were assumed to be common parameters between the data sets. If a single data set was used in fitting the equation, large deviations in the estimates for ka and .alpha. occurred as ka became < .alpha.. However, when multiple data sets were fit simultaneously, correct values for ka and .alpha. were consistently predicted regardless of the relative magnitude of the initial estimates.