Application of the NONMEM method to evaluation of the bioavailability of drug products.

The NONMEM method, one of the methods used for analysis of population pharmacokinetics, was applied to the evaluation of the relative bioavailability of drug products. The data of 2 x 2 crossover studies of several drugs and a 3 x 3 crossover study of phenytoin using healthy volunteers were analyzed by the NONMEM method, as well as by the confidence interval procedure, which is a standard approach to the bioequivalence test data using model-independent parameters. Very close confidence intervals for the relative difference in bioavailability were estimated by the NONMEM method and the standard approach, both in cases where products were bioequivalent and where they were not. The NONMEM method could also correctly estimate the relative bioavailability of the products using simulated clinical data obtained by randomly reducing the sampling points of the phenytoin data mentioned above, which cannot be analyzed by the standard approach. Thus, the usefulness of the NONMEM method was confirmed for evaluation of bioavailability using clinical or experimental data.