Experiences in the application of NONMEM to pharmacokinetic data analysis

Ethical issues arising from the use of patients in medical research have stimulated pharmacokinetic research in population kinetics, which requires only a few concentration samples of each individual. Using historical maprotiline data, the new approach of population kinetics was investigated and compared to individually estimated kinetics. Two different population kinetic methods were applied. The naive approach, a quick and dirty method, was compared to the nonlinear mixed-effects method, which was applied by the NONMEM package. Based on the results we obtained from actual maprotiline data as well as from simulated data, NONMEM is a reasonable tool for the estimation of population pharmacokinetic parameters. The main advantage of NONMEM over the naive approach lies in the possibility of obtaining standard deviations of random effects related to the variability between subjects.