The objective of this research was to evaluate how the use of mathematical models that simulate the drug's pharmacokinetic, can influence the calculation of pharmacokinetic parameters, being the human-computer-interaction an useful tool to simplify them. For it, we study the effect of P-gp inhibitors on the pharmacokinetics of the anticonvulsant, phenytoin; we co-administered the drugs to a group of rats and then measured the plasma concentrations of phenytoin, from which we calculated the pharmacokinetic parameters, manually and using the WinNonlin software. P-gp inhibitors caused a change in the pharmacokinetics of phenytoin, moving from the open-one compartment model to the open-two-compartment model, this was demonstrated with a better fit of data (r = 0.9871) in the two compartments model. Since complex mathematical models are necessary, the software will be useful, but it is the pharmacokinetic specialists who evaluate and define the model to be used, which demonstrates the importance of HCI.