Kinetics of drug transport and concurrent metabolism in human cell cultures I: theory.
A method for evaluating the passive permeability and single-step metabolism of drugs in suspension cultures of mammalian cells was formulated assuming linear kinetics. It was assumed that the metabolizing enzymes are driven by endogenous substrates present in steady-state quantities. The presence of the drug in radiolabeled tracer quantities was assumed to cause only a small perturbation from the endogenous steady-state operating point. The time course solutions for the drug and its metabolite are given in terms of macroscopic constants, and their physical interpretations are given in terms of metabolic and transport parameters.