Unlike predictive ADMET models described in other modules, Simulation Module features a special set of predictive models that are not statistical; in the sense of turning just molecular structures into direct property estimations. Module results are simulated, taking on input selected ADMET estimations, dose and predefined human physiology, and solving a deterministic, region-dependent system of differential equations. This system is based on the "Human-Physiological-Fasted" version of the ACAT model of drug absorption employed in its entirety by our software GastroPlus™ reflecting compounds' dissolution, permeation, transit and regional dependence along the intestinal tract. Users are advised to consult GastroPlus documentation on further details of the ACAT model.

Simulated fraction absorbed in human

SimHIA* models simulate oral fraction absorbed in human. The only formulation variable changing here is dose. By default, all other parameters come from ADMET predictions, but can be optionally replaced by experimental values per compound. In fact, the default four SimHIA* columns reflect four different doses: 1 mg (SimHIA_1), 10 mg (SimHIA_10), 100 mg (SimHIA_100) and 1000 mg (SimHIA_1000).

Simulated optimal dose in human

The SimDOSE (Simulated Optimal Oral Dose in Human) model in ADMET Predictor is used to assess oral dose levels, in mg, necessary to reach the desired unbound plasma concentration (C_eff) of drug candidates at steady state. The steady state is determined by SimDOSE model as a state where administration of additional dose does not lead to further increase in unbound "peak and trough" plasma concentrations. The model accounts for possible limitation of fraction absorbed due to low solubility or permeability of compound. Most of the model inputs are by default calculated by ADMET Predictor models (or descriptors) from molecular structure, but others must be supplied by user. The most important of these is the target effective concentration C_eff - the average unbound plasma concentration at steady-state. It must be supplied by the user in an input file, preferably in the form of per-compound auxiliary data. Another mandatory input is the total systemic clearance. Other inputs requiring user attention are precipitation time, initial guess of the optimal dose, dosing interval and volume, particle radius, particle density, and body weight.

For further information about licensing the ADMET Predictor Simulation module, please contact:

Mr. John DiBella
Director, Marketing & Sales
661-723-7723 ext. 244
john.dibella@simulations-plus.com