Expanded version of PKSIM for pharmacokinetic simulations of both metabolite and parent drugs.

: We recently described a computer software package for pharmacokinetic simulations called PKSIM. The programs are useful for studying drugs that display either a one-, two-, or three-compartment body model with linear or nonlinear elimination following single or multiple dosing. The practicality of PKSIM owes to its user-friendliness and flexibility to study the impact of pharmacokinetic perturbations and dosage regimens on the drug's concentration-time profile on a real-time basis. The interactive nature of PKSIM allows the test variables to be easily changed after each simulation. High-resolution graphic capabilities also permit presentation of pharmacokinetic profile in various body compartments, either individually or collectively on a single graph. The capability of PKSIM was recently extended to include simulations of both parent drug and metabolite, which adds to the value of the package. The present paper describes in detail the functions of these new features and how they can be applied to better comprehend the pharmacokinetic interdependency between the parent drug and metabolite. In addition to the dose, dosing regimen and rate of drug absorption, influences on the kinetic profiles of parent drug and metabolite by other variables such as formation rate of the metabolite, tissue distribution, tissue redistribution, elimination rates and distribution volume of both entities can be studied with minimal efforts. These new features can be particularly helpful for researchers to study prodrugs and drugs that produce active or toxic metabolites, or better understand the basic concepts of metabolite kinetics.