As a company with a strong academic foundation, our scientists actively publish the results of their research in the form of conference abstracts and peer-reviewed papers. We’re proud to announce that our PBPK modeling and simulation group has hit a milestone of having published more than 100 papers since 2007. In this blog post, I’ll discuss some of the highlights of this research group and touch on how our Consortium members are using the Simcyp Simulator to accelerate the pace of drug development.
What has been the focus of our publications?
Physiologically-based pharmacokinetic modeling (PBPK) approaches can predict the absorption, distribution, metabolism and excretion (ADME) of a drug. It enables drug developers to predict drug exposure levels based on patient and drug characteristics, and concomitant medications. It can fill knowledge gaps, especially where clinical data are scarce.
In the past year, our scientists in the Simcyp group have published heavily in the areas of biologics including monoclonal antibodies (mAbs), cardiac safety and drug transporters. Monoclonal antibodies and their derivatives are a rapidly growing segment of the pharmaceutical industry’s pipeline. In fact, more than 40 mAbs and derivatives have been approved for a variety of therapeutic applications and about 500 more are currently in different stages of development. Two recently published papers highlight how PBPK models are advancing the understanding of this important class of therapeutic drugs:
- Dr. Linzhong Li and colleagues published in the AAPS Journal, Simulation of Monoclonal Antibody Pharmacokinetics in Humans Using a Minimal Physiologically Based Model
- This group also published the CPT Pharmacometrics and Systems Pharmacology article, Incorporating Target Shedding Into a Minimal PBPK-TMDD Model for Monoclonal Antibodies.
Using virtual populations to study drug disposition in multiple life stages and subpopulations
We are entering the era of personalized medicine as exemplified by the launch of the Precision Medicine Initiative earlier this year. While clinical studies provide powerful insights into a drug’s safety and efficacy, there are both ethical and practical limitations to conducting clinical trials in children, pregnant women, and patients with organ impairment.
The Simcyp Simulator is an invaluable tool for studying the effects of drugs or toxins in multiple life stages and sub populations. The research contributions of our PBPK modeling and simulation group are significantly advancing our understanding of pediatric drug disposition. Some of the highlights in this area include:
- Dr. Jennifer Bonner’s paper in Biopharmaceutics & Drug Disposition “Does age affect gastric emptying time? A model-based meta-analysis of data from premature neonates through to adults.” (Hint: the answer may be “no” with meal type being a better predictor of gastric emptying time.)
- Dr. Trevor Johnson’s paper in the same journal “Development of physiologically based pharmacokinetic model to evaluate the relative systemic exposure to quetiapine after administration of IR and XR formulations to adults, children and adolescents“
- Dr. Farzaneh Salem’s paper in Clinical Pharmacokinetics “A Re-evaluation and Validation of Ontogeny Functions for Cytochrome P450 1A2 and 3A4 Based on In Vivo Data“
The Simcyp Simulator: the gold standard for PBPK modeling in scientific publications
We are also proud to see the large number of publications by our Consortium members that use the Simcyp Simulator. In the area of drug-drug interactions alone, Consortium members published eleven papers in the last year. Although we often focus on the potential hazards of interacting drugs, food effects can also be an important cause of altered pharmacokinetics. Two of these articles focused on predicting the extent and variability of the change in drug disposition caused by drinking grapefruit juice. Grapefruits and limes contain furanocoumarins which inhibit CYP3A4 enzymes. This can lead to an increase in the concentration of a drug and cause toxicity. For more information, you may want to read this Biopharmaceutics & Drug Disposition article by our academic associates at Keio University in Japan or this Journal of Pharmacology and Experimental Therapeutics article by our academic associates at my alma mater, the University of North Carolina at Chapel Hill.
All information presented derive from public source materials.
Learn more about the benefits of leveraging PBPK
To learn more about how sponsors are benefiting from Simcyp science, please read this case study on how a medium-sized biopharmaceutical company leveraged Certara’s trial simulation software and PBPK modeling and simulation consulting services to facilitate regulatory approval for a long-acting injectable anti-psychotic drug.