Multiexponential, multicompartmental, and noncompartmental modeling. I. Methodological limitations and physiological interpretations.

Multiexponential, multicompartmental, and noncompartmental analysis methods are conventional modeling tools in life science areas, and, on occasion, a number of facets of each are misunderstood, misused, or misinterpreted. We critically examine some of the assumptions, subtleties, and properties of each of these methodologies, with emphasis on their applicability and their interpretation in physiological terms. We discuss the similarities and differences in noncompartmental and compartmental approaches, their relationships with multiexponential models, and several important assumptions that must be satisfied in the practical application of these techniques. A key issue is the highly restricted structure of the noncompartmental model, limiting its applicability quite severely. Noncompartmental analysis is not model independent, as it is often called. Another issue is the importance and manner of choosing a suitable multicompartmental topology, consistent with system structure and modeling goals, when a physiological mapping of specific model parameters is desired.