What’s New in the Simcyp Simulator v17?
Conducting clinical trials incurs immense costs. Thus, technologies that inform and complement clinical trials represent a sea change in drug development. Sponsors and regulatory agencies routinely use physiologically-based pharmacokinetic (PBPK) modeling and simulation to assist in dose selection and inform product labeling.
PBPK models describe the behavior of drugs in different body tissues. Depending on the route of administration, the course of the drug can be tracked through the blood and tissues. Each tissue is considered to be a physiological compartment. The concentration of the drug in each compartment is determined by combining systems data, drug data, and trial design information. The systems data includes demographic, physiological, and biochemical data for the individuals in the virtual study population. The drug data consists of its physicochemical properties, its binding characteristics, and information on its metabolism and solubility. The trial design information comprises the dose, administration route, dosing schedule, and co-administered drugs.
The Simcyp® Simulator links in vitro data to in vivo ADME (absorption, distribution, metabolism, and excretion) and pharmacokinetic/pharmacodynamic (PK/PD) outcomes to help explore potential clinical complexities prior to human studies and support decision-making in drug development.
Watch this webinar with Nikunjkumar Patel, Oliver Hatley, and Matthew Harwood to learn how the latest updates in the Simcyp Simulator v17 will help provide insights that support developing safer, more effective medications. These enhancements include:
- Expansion of Populations Library: Cancer patients differ from healthy people in terms of their demographics and their abundances of blood plasma binding proteins and hepatic transporters. These changes can mean that the pharmacokinetics of a drug may be altered in this population. The Simcyp Simulator v17 includes a new virtual cancer population as a generic population template for modeling PBPK in oncology.
- Multi-phase Multi-layer (MPML) Mechanistic Dermal (MechDermA) Model: The ability to estimate systemic exposure from dermal absorption is essential in developing new dermatological medications or assessing the toxicological liability of commercially-used chemicals. The previous dermal model in the Simcyp Simulator was based on the skin physiology of healthy male and female Caucasian subjects. As part of a multi-year FDA grant, the model has been enhanced to include pediatric and geriatric populations, additional ethnic groups, and specific skin diseases such as psoriasis. All major topical and transdermal delivery systems can be simulated. The model also allows identification of clinically relevant critical product quality attributes which can aid product specification. In addition, a vehicle evaporation model has been added to the MPML― the MechDermA model― to account for the effect of vehicle evaporation on dermal drug absorption from topical formulations.
- Expansion of Gut Transporters and IVIVE Techniques in the ADAM/M-ADAM Models: Drug transporters play a vital role in governing drug concentrations in the blood, liver, brain, intestine, lung, and kidney. Transporter protein-mediated drug-drug interactions (DDIs) can cause loss of drug effectiveness and toxicity. To gain greater insights into the role of transporters in PK/PD and toxicity, an additional 14 gut transporters have been added to the Advanced Dissolution, Absorption and Metabolism (ADAM) and Multi-layer ADAM (M-ADAM) models with the ability to scale to in vivo via both relative and absolute transporter abundances utilizing the appropriate intestinal membrane based scaling factors.