Certara, a Princeton, N.J.-based global technology-enabled drug development and drug safety consultancy, has released version 14 of its Simcyp Population-based Simulator, which enables biopharmaceutical researchers to predict drug-drug interactions and pharmacokinetic-pharmacodynamic (PK-PD) outcomes in virtual human and animal populations.

The Simcyp Simulator can be used to select ideal dosing regimens, determine drug-drug interactions and predict PK changes in special populations, such as neonates, pregnant women or patients with renal impairment who receive multiple drugs, in order to inform study design and guide appropriate labeling language.

Simcyp whole body simulation methodology can predict the pharmacokinetics of drug compounds and proteins based on in vitro data. The simulator includes a unique set of genetic, physiological and epidemiological databases that facilitate the simulation of virtual populations from around the globe.

The Simcyp Simulator’s ADAM (Advanced Dissolution Adsorption Metabolism) module now contains extended features for handling fed versus fasted oral absorption models, which take account of some of the more complex food effects such as changes in viscosity. In addition, its Mechanistic Permeability (Mech Perf) human model can estimate drug permeability in different regions of the gastrointestinal (GI) tract, including the colon. Physiologically-based (PB) PK mechanistic models are playing an increasingly important role in regulatory submissions to the FDA.

A Nested-Enzyme-Within-Enterocyte (NEWE) model has been added to the simulator which takes into account the enterocyte turnover in the gut wall and the resulting changes in the level of intestinal drug metabolizing enzymes. Clients can now estimate a value for the proportion of unbound drug in the gut wall based on the physiological chemistry and blood-binding capabilities of the drug and the tissue composition of the gut wall. This unique mechanistic model allows the Simcyp Simulator to more closely mimic the actual interactions of drugs with gut wall enzymes during the absorption process.  

In addition to providing compound files, Certara also creates defined patient populations to expedite virtual clinical trials. For example, the Simcyp Simulator has virtual populations based on ethnicity such as Japanese or Chinese, and specific physiological conditions, including pregnant women, patients with various severity of cirrhosis and those with different levels of renal impairment.  

Clients increasingly want their in-silico and virtual trials to match what they will do in the real clinical trials more closely. They want to mirror the complex dose scheduling and combinations in the form of administration. If the initial dose will be given as an injection and then followed by tablets, they want the same to happen in the virtual trial. In addition to providing that capability, the simulator now also gives clients the option of injecting drugs into specific organs and following the kinetics using the PBPK model.

Clients can now monitor two drug metabolites at the same time without having to repeat the simulation. As drug metabolites can play significant roles in some aspects of drug safety and pharmacological response, this is a very practical addition to the platform.