Artificial neural networks as a novel approach to integrated pharmacokinetic-pharmacodynamic analysis.

A novel model-independent approach to analyze pharmacokinetic (PK)-pharmacodynamic (PD) data using artificial neural networks (ANNs) is presented. ANNs are versatile computational tools that possess the attributes of adaptive learning and self-organization. The emulative ability of neural networks is evaluated with simulated PK-PD data, and the power of ANNs to extrapolate the acquired knowledge is investigated. ANNs of one architecture are shown to be flexible enough to accurately predict PD profiles for a wide variety of PK-PD relationships (e.g., effect compartment linked to the central or peripheral compartment and indirect response models). Also, an example is given of the ability of ANNs to accurately predict PD profiles without requiring any information regarding the active metabolite. Because structural details are not required, ANNs exhibit a clear advantage over conventional model-dependent methods. ANNs are proved to be robust toward error in the data and perturbations in the initial estimates. Moreover, ANNs were shown to handle sparse data well. Neural networks are emerging as promising tools in the field of drug discovery and development.