Physiologically-based pharmacokinetic (PBPK) modeling is a technique used to predict the absorption, distribution, metabolism, and excretion (ADME) of chemicals in both humans and animal populations. The use of PBPK modeling and simulation has increased in all stages of the drug development process and can be utilized in new drug applications. With the release of the Simcyp Discovery Simulator, scientists can utilize PBPK modeling earlier in the drug discovery and development process and can make better informed decisions to reduce the risk of drug failure.
Below, we’ll discuss how the Simcyp Discovery Simulator accelerates early drug development.
What is Simcyp Discovery Simulator?
The Simcyp Discovery Simulator is a new PBPK software created for scientists working in small molecule drug discovery and translational research. The software includes PBPK models for mouse, rat, dog, monkey, and humans. This allows scientists to predict first-in-human (FIH) pharmacokinetics and enables a better understanding of how investigational drugs may perform in the body prior to clinical trials.
Drug-drug interactions (DDIs) are a potential cause of drug removals from the market. Scientists are now able to predict DDI risk before moving forward into clinical development. The Simcyp Discovery Simulator flags potential DDIs using the built-in static DDI calculator. Based on various regulatory guidances, the calculator highlights potential metabolic- and transporter-mediated drug interactions.
Rationale for using Modeling and Simulation to inform early drug development
Modeling and simulation has become paramount to the drug development process. Using modeling and simulation, scientists can utilize data and knowledge to make informed critical decisions. These insights can be used to design more efficient clinical trials, ultimately helping scientists to determine the right dose and formulation for individuals.
Incomplete knowledge of the drug and lack of understanding of the exposure-response relationship are a few reasons why clinical trials fail. These can be addressed by modeling and simulation. The FDA supports the use of modeling and simulation in the drug development process. With the knowledge gained from modeling and simulation, safer drug therapies can be brought to the market faster and have a higher probability of market success.
How will this affect early-stage development and the drug approval pipeline?
Simcyp Discovery can help mitigate some of the challenges that plague the drug development process. One of those challenges is the high drug failure rate of investigational drugs during the pre-investigational new drug (IND) process. Simcyp Discovery provides rapid batch screening to help identify the best drug candidates to lower the risk of drug failure related to PK and DDI. This allows scientists to prioritize continued research on the drug candidates that have the best chance of success, thus reducing the likelihood of drug failure.
PBPK modeling and simulation can also be used to address formulation issues earlier in the drug development process. Poor absorption can be caused by solubility, particle size, dissolution, and permeability limitations. Sensitivity analyses can be performed using Simcyp Discovery to explore the key drivers of poor absorption and help design more effective formulations, potentially expanding the number of patients who can benefit from the therapy.
To learn more about the Simcyp Discovery Simulator and its uses, watch the demo video.