Rosa Announces Qualification of a Novel Methodology for Prediction of Pediatric Clinical Pharmacology Data in Bile Acid Metabolism

Rosa & Co. LLC, a drug development advisory firm with expertise in drug-disease modeling and simulation, today announced the novel results and qualification of a new Bile PhysioPD model. The model and results were presented at the 2011 American Conference on Pharmacometrics, San Diego, CA. The Bile PhysioPD model was developed to investigate bile acid metabolism and cholestasis in adult and pediatric populations. It was based entirely on literature data, including a rich set of metabolomics and genomics data. This is one of the first known models to effectively incorporate these types of data sets into a physiological model.

The Bile PhysioPD Model was qualified using Rosa’s Model Qualification Method, which was also presented at the American Conference of Pharmacometrics, 2011. This literature-based model was used to predict the pharmacokinetics (PK) of ursodiol in pediatric patients. Ursodiol pharmacokinetics is closely related to efficacy in this population. The predicted results were compared to the results from a pediatric clinical trial that implemented a population pharmacokinetic modeling analysis of plasma ursodiol concentrations measured with Accelerator Mass Spectrometry (AMS). The results from the physiological modeling were an excellent match to those derived from the NONMEM population PK model.

In addition, the Bile PhysioPD model was able to identify specific genes and biologic mechanisms that are most likely to cause the observed inter-individual variation in PK data. This insight would not be achievable with classic PK modeling, because classic modeling relies on clinical data and does not explicitly represent biological mechanisms.

Results from both types of models are currently applied to developing methods for dose predictions and facilitating drug approval for pediatric populations. The PhysioPD modeling methodology can be focused on adults or pediatrics, and it is broadly applicable across disease areas.
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“This is an important development. It’s especially exciting, given the paucity of methods we can apply to our youngest and most vulnerable patients: premature and term neonates” commented Alexander A. Vinks, Professor of Pediatrics & Pharmacology at the University of Cincinnati.

"The Bile PhysioPD model allows for more efficient studies in newborns, with fewer samples required to monitor bile acids. It is a significant step toward individualized therapy in our most vulnerable patient group” said Dr. Toufigh Gordi, President of PK/PD and Clinical Pharmacology Services and coauthor of the work. “More generally, the validation results show that PhysioPD models, even in the absence of clinical data, can predict clinical results and identify both genetic and biologic mechanisms that cause population variability.”

About Ursodiol
Ursodiol (ursodeoxycholic acid; UDCA) is a mimetic of an endogenously produced bile acid, and it is approved to treat cholestasis in adults; it is also frequently used off-label to treat neonatal cholestasis. Cholestasis, or a reduction of the normal flow of bile from the liver to the small intestine, is a common affliction of premature neonates admitted to the neonatal intensive care unit. The mechanism of action of ursodiol for treatment of cholestasis in neonates is unknown, and its efficacy varies widely from patient to patient. The PK of UDCA in neonates and the causes of its wide variation in efficacy had never been characterized, because measurement of ursodiol required differentiating between endogenous and exogenous compounds. AMS methodology overcomes the measurement difficulty, and modeling has provided a method to identify potential causes of variability.

About Rosa
Rosa informs our customer’s most critical decisions – from preclinical through clinical development – with the creation and use of mathematical models that simulate disease physiology, drug action, patient variability, and trial outcomes. To address the full spectrum of related issues, Rosa offers two customized approaches: classic pharmacokinetic/ pharmacodynamic (PK/PD) models and Rosa’s innovative PhysioPD™ models. With these approaches, Rosa’s clients collaborate in model creation and testing, retain the final model, and acquire the ability to use it and understand its implications for their drug development programs. Rosa’s staff have close to two decades of unparalleled professional experience in using drug-disease modeling and simulation (M&S) to accelerate drug development; they have covered hundreds of applications with dozens of clients. The Rosa team is unique in their breadth and depth of disease area experience, which includes metabolic and cardiovascular diseases, oncology, gastro-intestinal disease, inflammatory diseases, immune dysfunction (including rheumatoid arthritis), pain, skin conditions, respiratory disorders, and antibacterials/antivirals. For more information, visit www.rosaandco.com.

Rosa & Co. LLC
751 Laurel St., Ste. 127,
San Carlos, CA 94070

This release was published on openPR.