PK-Sim® Modules

Modular design offers flexible handling of pharmacokinetic research projects

All three PK-Sim^® software packages are designed within a modular architecture and contain the following entities (click here to view enlarged picture of modules integrated in the respective PK-Sim^® packages):

Species Modules Absorption Modules Distribution Modules Metabolism & Excretion Modules PK-PD Module PK-Pop Module Clearance Scaling Module

Depending on the package purchased these modules are either integrated or can be upgraded at any time. For extending your PK-Sim^® version just contact our technical support.

PK-Sim^® can simulate the pharmacokinetics in five different species (mice, rats, dogs, monkeys and humans). Availability of the species depends on the license that was purchased. In the PK-Sim^® Research package only rat and human can be selected as species. In both the PK-Sim^® Pre-Clinical and the PK-Sim^® Clinical package all species are available.

Since PK-Sim^® version 3.0 this module has been available as a basic element implemented in all three PK-Sim^® packages. The Absorption Module simulates the gastro-intestinal transit and absorption process and serves the needs of scientists involved in biopharmaceutics and formulation development. It is possible to simulate active transport in the intestine (transmembrane influx or efflux, Pgp-like efflux) as well as metabolism processes (multiple linear or saturable Michaelis-Menten) taking place in the gut wall. Furthermore, different release kinetics (e.g. for controlled release) can be modeled selecting different predetermined or user definable release functions for oral application.

Model parameters (organ/plasma partition coefficients, permeabilities) are calculated from substance specific input parameters and can be adjusted independently. Since version 4.0 of PK-Sim^® the Rodgers and Rowland Model for a more accurate prediction of partition coefficients of ionized compounds is included. This model takes electrostatic interactions of drugs with acidic phospholipids present in the cellular membrane into account, which is the reason why pK and pH values are included in the calculation of partition coefficients.

Multiple metabolism and elimination processes in various organs and compartments can be simulated using this add-on module. For example, biliary excretion can be described, allowing a realistic description of drugs that are subject to enterohepatic circulation.

This module is an extension of PK-Sim^® enabling the description of pharmacodynamic effects and thus the simulation of dose-response relationships. As in conventional PK-PD modeling, a pharmacodynamic effect in dependence of the drug concentration can be defined. Simulated concentration-time profiles for all organs are obtained, in addition to experimental plasma profiles, which particularly help researchers during the late optimization phase and preclinical development to identify specific effects (e.g. the relevance of active transport processes) and to guide the experimental efforts, saving time and money.

The PK-Pop module allows for the creation and simulation of a realistic virtual population to assess the pharmacokinetic variability in a group of humans. At the heart of this module are built in databases containing information about the age and gender dependence of mean values and variability of the relevant anatomical parameters such as body size, organ volume and blood flow (e.g. from the US NHANES III study).

With this module hepatic, renal and biliary clearances in a child under the age of 18 years can be estimated based on information about clearance values in adults. In vitro ontogeny information as well as in vivo data of compounds, which undergo elimination by a single process, were used to build the clearance scaling module.