Systems approach to the study of drug transport across membranes using suspension cultures of mammalian cells. I. Theoretical diffusion models.

Some general physical models are described for the diffusional transport of drugs across membranes of cells in culture suspensions. The models provide a basis for the design and analysis of experiments that are aimed to describe (a) the nature of the principal transport barrier, (b) the kinds of drug species being transported, (c) whether, where and how much solute binding occurs, and (d) the influences of pH, partition coefficient and numerous other factors. The cell is treated as a sphere with non-homogeneous phase compartments. Both rigorous and approximate mathematical expressions have been derived for the quasi-steady-state diffusion through the membrane followed by three cases accounting for the distribution of drug jn the heterogeneous cell interior, that is, (a) the non-steady-state situation, (b) establishment of instantaneous distribution and (c) instantaneous distribution in the aqueous interior with slow permeation of drug into the cytoplasmic bodies and nucleus.