Researchers using GastroPlus for physiologically-based pharmacokinetic (PBPK) simulations can get results for a 24-hour simulation in about 5 seconds, depending on the drug.
In PBPK simulations, each tissue is modeled independently to provide better animal-to-human scaling, better initial estimates of distribution of drug into various tissues, and total volume of distribution for new compounds, Woltosz says.
Simulation Plus Admet Predictor, updated in June with version 1.2.0, allows researchers to predict some 50 different properties from molecular structure. It is used for very high throughput in silico screening of large compound libraries and for estimates of key properties for single compounds. By using groups of artificial neural networks and averaging their outputs, it predicts properties critical to oral absorption as well as several pharmacokinetic properties and types of toxicity.
It has models for the maximum recommended therapeutic dose, estrogen receptors, toxicity in fathead minnows, tumor formation in rats, tumor formation in mice, and bacteria mutagenicity (the Ames test) and is working on four others that remain confidential.
Admet Modeler, also released in June, allows researchers to build structure-property models from their own data on their own servers and add them to Admet Predictor models, thus keeping the information in-house.
The technology combines automatic filtering and selection of descriptions, compound clustering for selection of training and test sets, and training a matrix of artificial neural net ensembles. The user selects the best ensemble for the final predictive model and sends it to Admet Predictor so it becomes a permanent new property prediction, enterprise-wide.
Simulations Plus released DDDPlus simulation software last spring for in vitro dose disintegration and dissolution studies for formulation scientists. Formulations for new active ingredients require only one calibration experiment before the software will predict how formulation changes affect the dissolution rate.
The application is similar to GastroPlus, but is only concerned with chemistry and physics, Woltosz says. The value occurs when you have such formulation changes as variations in amounts of active ingredients, excipients, and particle sizes. The program helps researchers simulate such changes and get results literally in seconds, he says.
MembranePlus, a similar product, is expected by years end to simulate and interpret Caco-2 and PAMPA in vitro membrane permeability. You can run exactly the same [physical] experiments in two different labs and get numbers that are 100 times different. With the simulation, you can understand the cause of these differences, Woltosz says.