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Simcyp Soars at 2020 AAPS Meeting

By Ellen Leinfuss

AAPS PharmSci 360 meeting took place virtually over the past week.  Not to be too ‘punny,’ but virtual drug development using mechanistic modeling took a prominent role on the agenda.  Fittingly (sorry, I am on a roll), the Simcyp Simulator accounted for 10 posters in the Physiologically-Based Pharmacokinetic (PBPK) group—leading the category. Of the 10, five were authored by Simcyp R&D scientists. Here is the list of topics and author affiliations. 

Simcyp posters

  • Predicting Local and Systemic Piroxicam Concentrations Following Topical Application using PBPK Modelling
    • This case study demonstrated the utility of the Simcyp MechDermA™ model for predicting both systemic and local concentrations of topically applied drugs. Parameters describing the Q2 and Q3 of these formulations can be input to the model and the effect of changes in these parameters can be simulated to assess Virtual Bioequivalence.
  • Integrating Drug Product Quality Attributes in a Bottom-Up PBPK Model to Simulate In Vitro Skin Permeation of Acyclovir Commercial Formulations
    • A mechanistic “bottom-up” PBPK model was developed that integrated drug product quality attributes to predict in vitro permeation of acyclovir commercial creams, following application on excised human skin. The model was used to understand the role of propylene glycol (PG) in the skin permeation of acyclovir from the Zovirax® Cream which contains 40% w/w PG.
  • Simulating Polymer Controlled Drug Release from Amorphous Solid Dispersions within a PBPK Framework: Case Example Ritonavir Norvir® Tablet
    • Dissolution of amorphous solid dispersions (ASD) under non-sink conditions is complex, with the possibility of several phase transitions within the dissolving medium and the ASD matrix. We used Simcyp to model polymer-controlled drug release from ASDs using a Particle Population Balance (PPB) model, which enables simultaneous consideration of release from two moieties / solid states from the dosage form.
  • Comparison of PBPK Models for Evaluation of Clinical PK Exposure and Drug-Drug Interactions with the CYP3A4 Inhibitor Itraconazole
    • PBPK models are often used to simulate clinical drug-drug interaction (DDI) studies. Itraconazole (ITZ), is a strong and selective inhibitor of CYP3A4, commonly used in DDI studies. ITZ can be administered as either a capsule or solution in both the fasted and fed state; therefore, PBPK models need to be flexible to account for the different dosing regimens. This current work compares three models for their predictive performance against 34 clinical pharmacokinetic studies and 24 clinical DDI studies.
  • Does Drug-Lipid Binding Add Up? A Surface Plasmon Resonance Study into Combined Phospholipid Liposome Binding and the Impact of Cholesterol
    • Understanding lipid binding is essential not only for appreciation of drug volume of distribution but also defining drug disposition and elimination in general.  However, binding studies are often conducted with one or two lipids, rather than a membrane surrogate comprised of different phospholipids, which could be more representative of the binding that occurs in vivo. This poster evaluates drug binding to different mixtures of phospholipids using PBPK.

Partner posters

  • PBPK Model Based Virtual Bioequivalence Assessment of Different Elagolix Formulations to Support Regulatory Biowaiver—AbbVie
    • Combining in vitro and in silico (PBPK) data enabled the development and evaluation of new formulations and achieving virtual bioequivalence without the need for clinical trials.  Analysis also identified permeability as determinant in elagolix absorption, thereby explaining the differences between in vivo versus in vitro dissolution profiles.
  • Investigation of the Oral Absorption of Azithromycin in Adults and Paediatrics Based on PBPK Modeling—University of Bath, University of Athens
    • The BCS classification of azithromycin is not clear, driving this study to identify the critical variables that influence the oral absorption of the drug in adults and paediatrics. The PBPK modeling approach revealed that permeation through the gut wall is the key driver of azithromycin oral absorption in both adults and paediatrics.
  • Can Exenatide ER be Administered Every Four Weeks? PBPK Analysis Supporting Dosage Regimen Change—California Northstate University, College of Pharmacy
    • The goal was to develop a pharmacokinetic model of exenatide to support the proposed dosage regimen change for an extended release formulation, from once weekly to every four weeks based on a recent study.  The model demonstrated the four-week regimen, which can potentially improve patient compliance by decreasing the frequency of administration and reducing the burden of health care costs.
  • Investigation of Changes in Pimavanserin Pharmacokinetics (PK) in Patients Suffering from Child Pugh A (mild), Child Pugh B (moderate), and Child Pugh C(severe) Hepatic Impairment—Millburn HS, Husson University, College of Pharmacy
    • The Simcyp hepatic cirrhosis population library is a semi-mechanistic model that predicts the effect of liver cirrhosis on drug clearance. PBPK modeling pimavanserin showed that drug exposure was about 1.5 -3.5-fold higher in liver cirrhosis patients aged 50-65 years old and 2-5 times higher in liver cirrhosis patients aged 66 – 95 years old. For all simulated patient groups, a dose reduction from the typical 34 mg is required for pimavanserin administration.
  • A Potential Method to Adjust Kp Scalar in Different Species for PBPK Modeling—Marshall B Ketchum University, College of Pharmacy
    • There is no specific trend in the Kp scalar in rats, dogs, and humans indicating it is generally hard to find a universal Kp scalar for all species.  This poster uses PBPK to support the identification of a universal Kp scalar for interspecies extrapolation.  Such information could greatly increase precision as well as reduce the time and cost of clinical trials.

For a review of all posters, visit

About the author

Ellen Leinfuss
By: Ellen Leinfuss
Ellen Leinfuss serves as SVP and Chief Commercial Officer for Certara’s Simcyp Division. Simcyp is the global leader in mechanistic modeling, which includes the renowned Simcyp Simulator for physiologically based pharmacokinetics (PBPK) and its Quantitative Systems Pharmacology (QSP) immunogenicity, immune-oncology, vaccine and gene therapy modeling & simulation platforms. Ellen has been at Certara for the past seven years, serving for many years as Chief Marketing Officer for the corporation. With a degree in chemistry and MBA in marketing, Ellen has provided management, business development and marketing leadership to organizations in the biopharmaceutical, environmental and energy fields. She is a published author and speaks regularly on topics related to model-informed drug development.

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