Use of the circuit simulation program SPICE2 for analysis of the metabolism of anticancer drugs.

Complex networks of biological processes are analogous to electrical circuits. For each step in a biological or electrical network, flow is dependent on the driving force and the conductivity of the step. The relationship between biological flows and their driving forces can therefore be expressed as relationships between analogous currents and voltages. The time dependence of approach to equilibrium or a steady state is determined by the rates of depletion of material in various compartments. Electrical capacitance is therefore analogous to compartment volume. Once these generalized concepts of flow, force and capacitance are recognized, it becomes clear that computer programs designed for analysis of electrical circuits may be used for simulation of biological networks. A set of simple mathematical descriptions of the individual steps and a diagram showing how the steps are arranged with respect to each other are all that is necessary to perform a simulation; there is no need for computer programming skills or differential equations. The use of SPICE2 for simulation of the cellular and plasma pharmacokinetics of cytosine arabinoside (araC) is described as an example. A network model is developed which considers cellular pharmacokinetics (membrane transport, intracellular phosphorylation and dephosphorylation), and plasma pharmacokinetics following infusions of araC.

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