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.
Join 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.
About Our Speakers
Nikunjkumar Patel is a principal scientist in Certara’s modeling and simulation group where he is heavily involved in oral and dermal absorption modeling projects and is a member of the Cardiac Safety Simulator development team. He joined Certara in August 2011 and led the development of the physiologically based IVIVC (PB-IVIVC) module of the Simcyp Simulator and the Pharmaceutics module of the SIVA (Simcyp In Vitro (data) Analysis) platform. Before joining Certara, he spent three years at the life science innovation labs of Tata Consultancy Services as a research scientist mainly working on pharmacokinetic/pharmacodynamic modelling and QSAR development for various ADMET properties. During his graduate studies, he used computer aided drug design (CADD) and molecular modeling to identify safe and potent novel anti-diabetic ligands.
Matthew Harwood is a senior research scientist at Certara. He obtained his Bachelor’s and Master’s degrees in Physiology and Human Nutrition from The University of Sheffield and his PhD from The University of Manchester. His early career involved undertaking nutritional and enterocyte transport research in Cystic Fibrosis at Sheffield Children’s Hospital. Since 2007, Matthew has been working for Certara and is principally involved in the development of human PBPK models developing models for incorporating enzymes and membrane transport proteins, and pre-clinical transporter protein knock-out PBPK models. He has a keen interest in ADME transporter proteomics with respect to translation into IVIVE-PBPK strategies.
Oliver Hatley is a senior research scientist who has been working at Certara since 2013. He obtained his PhD investigating in vitro-in vivo extrapolation of intestinal metabolism from the Centre for Applied Pharmacokinetic Research (CAPKR) at the University of Manchester. Oliver is part of the translational sciences in DMPK group within Simcyp and has led development of the esterase organ and blood in vitro-in vivo scaling strategies. He is also involved in the development of special populations within the Simcyp Population-based Simulator.