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Simcyp™ Compound Summaries Library: What is it & why should you use it?

In the world of pharmacokinetic/dynamic (PBPK/PD) modelling, compound PBPK models are incorporated into compound files that serve as a vital component for accurate predictions for virtual clinical trials. Version 22 of the Simcyp PBPK Simulator boasts an extensive library of 130 small molecule and 6 large molecule compound models, encompassing enzyme and transporter substrates, inhibitors, inducers, and drug metabolites. Besides these models, the Simcyp Members Area contains more than 100 published PBPK models for various compounds, created by consortium members, academic groups, regulatory agencies, and Certara researchers. Many clinical scenarios can be simulated using these compounds, based on their pharmacokinetic and pharmacodynamic properties.


The Simcyp Compound Library is composed of a mix of drug metabolites, and drugs that are DDI victims and perpetrators.
Composition of Simcyp compound library.

Development and Verification: Building PBPK compound models within the Simcyp Simulator is a meticulous process that requires in-depth analysis and extensive verification. Detailed compound summaries are provided for each compound, offering insights into how Certara scientists develop and verify each one. The summaries provide an overview of the structural models employed in the overall PBPK/PD model as well as a comparison of the compound file performance against observed data.

Model performance Verification: The compound summaries highlight various performance metrics. Simulations of concentration-time profiles, trial statistics (such as Tmax, Cmax, AUC, and clearance), clinically reported drug-drug interactions (DDIs) and pharmacodynamic effects provide a comprehensive understanding of each compound’s behavior. The compound summaries also include more than five hundred reported clinical pharmacokinetic (PK) profiles and over 500 DDIs, considering demographic factors such as gender, age, and ethnicity.

Input Parameters and Absorption Models: Each compound summary contains a detailed table of model input parameters. Physicochemical information about the drug such as its molecular weight, compound type, pKa, and logP is included within these tables. Additionally, the summaries provide model input parameters for absorption, elimination, and interaction. There are three absorption models available in the Simcyp Simulator: first order (FO), advanced dissolution, absorption, and metabolism (ADAM), and multi-layer ADAM (M-ADAM). The Mechanistic Permeability (MechPeff) and regression-based permeability prediction models are both effective models for predicting regional permeability of drugs. The compound library contains a diverse range of compounds developed using different absorption and permeability models.


The Simcyp Compound Library is composed of a mix of drug metabolites, and drugs that are DDI victims and perpetrators.
Overview of absorption models used within the compound library. FO: first order; ADAM: Advanced Dissolution, Absorption, and Metabolism

Distribution Models: Simcyp offers two options for modeling drug distribution: minimal and full PBPK. There are three compartments in the minimal PBPK model: the systemic, the portal vein, and the liver. The minimal PBPK model uses single adjusting compartments (SACs) to capture observed clinical PK profiles. For organs like the brain, kidneys, lungs, and skin, the full PBPK model allows incorporating mechanistic permeability-limited multi-compartment organ models.

Enzymes and Transporters: Understanding drug elimination and drug-drug interactions is essential for modern PBPK modeling. The Simcyp Simulator covers a wide range of elimination inputs. The elimination pathways within the Simcyp Simulator include enzyme kinetics, such as those for Cytochrome p450s (CYPs), UDP-glucuronosyltransferases (UGTs), and others, derived from in vitro or in vivo studies. Most library files incorporate CYP-mediated metabolism. There are also transporter kinetics considerations, with 17% of compounds including models for gut, kidney, and liver transporters. The Simcyp Simulator takes these details into account to ensure accurate estimation of drug metabolism and interactions.

Validation of Kinetics and Interactions: Over 500 clinical drug-drug interactions (DDIs) from 319 publications have been utilized to validate the kinetics and interactions inputs. There are four DDI mechanisms available in the Simulator: competitive inhibition, mechanism-based inhibition, induction, and suppression. Competitive inhibition is the mechanism for a majority (57%) of modeled DDIs reported in the compound summaries thus emphasizing its clinical importance in DDIs.

The Value of Compound Summaries: Compound summaries provide drug developers with insight into the production of compound files, the selection of structural models, and their performance verification. As a result, these reports offer ready-made qualification/performance verification documents for interactions with regulatory authorities.

Discover the power of the Simcyp compound library and join numerous sponsors who have leveraged these compound summaries to strengthen and speed up their regulatory submissions for investigational.  

For guidance on developing your own PBPK compound files in the Simcyp Simulator, please watch this video:

About the authors

Liam Curry
By: Liam Curry

Liam Curry is a research scientist at Certara UK. He received his Master’s degree in pharmacology from the University of Nottingham where his work focused on ion channel modulation.

Liam is part of the translational sciences in DMPK group within the Simcyp division and has been involved in the development of compound files and expansion of the mechanistic kidney model. He is also concerned with the automation of compound/population summary production using R/LaTeX, refinement of the Simcyp Report Assistant and forms part of the Simcyp data management team.

Erika Brooks
By: Erika Brooks

With over 22 years of experience in hospitals, health systems, associations, life sciences, physician practices, and suppliers, Erika is an experienced marketing strategist and supports the Simcyp offering with Go-to market planning and execution.