Pharmacokinetic–pharmacodynamic modelling and simulation using the electrical circuit simulation program spice2

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Abstract
The use of the electrical circuit simulation program SPICE2 for performing digital computer simulations of linear and non-linear pharmacokinetic–pharmacodynamic models is described. SPICE2 utilizes the principles of network thermodynamics (thermodynamics of electrical circuits). These principles dictate analogy between the conservation laws of chemical reactions and mass transport and Kirchhoff's laws of current and voltage balance, and also prove that Fick's law of diffusion is isomorphous with the conductance form of Ohm's law. Detailed descriptions of program inputs, formats, and options for simulation of linear and non-linear pharmacokinetic–pharmacodynamic systems are provided, with appropriate examples. Single as well as multiple dose simulations (accumulation kinetics and dynamics) are discussed. The advantages of SPICE2 over other available simulation packages, including user-friendliness, ease of operation, versatility, power, and the economy of time and effort afforded, are emphasized. The educational value of SPICE2 as a highly versatile tool for teaching both fundamental and complex pharmacokinetic–pharmacodynamic concepts, as well as its routine usage in elucidating complex research problems, are also discussed.