Search results for " MODELLI"
showing 10 items of 1472 documents
A measurement of material in the ATLAS tracker using secondary hadronic interactions in 7 TeV pp collisions
2016
Knowledge of the material in the ATLAS inner tracking detector is crucial in understanding the reconstruction of charged-particle tracks, the performance of algorithms that identify jets containing b-hadrons and is also essential to reduce background in searches for exotic particles that can decay within the inner detector volume. Interactions of primary hadrons produced in pp collisions with the material in the inner detector are used to map the location and amount of this material. The hadronic interactions of primary particles may result in secondary vertices, which in this analysis are reconstructed by an inclusive vertex-finding algorithm. Data were collected using minimum-bias trigger…
Stochastic description of traffic breakdown
2003
We present a comparison of nucleation in an isothermal-isochoric container with traffic congestion on a one-lane freeway. The analysis is based, in both cases, on the probabilistic description by stochastic master equations. Further we analyze the characteristic features of traffic breakdowns. To describe this phenomenon we apply the stochastic model regarding the jam emergence to the formation of a large car cluster on the highway.
Formulation predictive dissolution (fPD) testing to advance oral drug product development: an introduction to the US FDA funded ‘21st Century BA/BE’ …
2018
Over the past decade, formulation predictive dissolution (fPD) testing has gained increasing attention. Another mindset is pushed forward where scientists in our field are more confident to explore the in vivo behavior of an oral drug product by performing predictive in vitro dissolution studies. Similarly, there is an increasing interest in the application of modern computational fluid dynamics (CFD) frameworks and high-performance computing platforms to study the local processes underlying absorption within the gastrointestinal (GI) tract. In that way, CFD and computing platforms both can inform future PBPK-based in silico frameworks and determine the GI-motility-driven hydrodynamic impac…
In vivo methods for drug absorption - comparative physiologies, model selection, correlations with in vitro methods (IVIVC), and applications for for…
2013
This review summarizes the current knowledge on anatomy and physiology of the human gastrointestinal tract in comparison with that of common laboratory animals (dog, pig, rat and mouse) with emphasis on in vivo methods for testing and prediction of oral dosage form performance. A wide range of factors and methods are considered in addition, such as imaging methods, perfusion models, models for predicting segmental/regional absorption, in vitro in vivo correlations as well as models to investigate the effects of excipients and the role of food on drug absorption. One goal of the authors was to clearly identify the gaps in today's knowledge in order to stimulate further work on refining the e…
IMI – Oral biopharmaceutics tools project – Evaluation of bottom-up PBPK prediction success part 2: An introduction to the simulation exercise and ov…
2016
Orally administered drugs are subject to a number of barriers impacting bioavailability (Foral), causing challenges during drug and formulation development. Physiologically-based pharmacokinetic (PBPK) modelling can help during drug and formulation development by providing quantitative predictions through a systems approach. The performance of three available PBPK software packages (GI-Sim, Simcyp®, and GastroPlus™) were evaluated by comparing simulated and observed pharmacokinetic (PK) parameters.Since the availability of input parameters was heterogeneous and highly variable, caution is required when interpreting the results of this exercise. Additionally, this prospective simulation exer…
Oral biopharmaceutics tools – Time for a new initiative – An introduction to the IMI project OrBiTo
2013
OrBiTo is a new European project within the IMI programme in the area of oral biopharmaceutics tools that includes world leading scientists from nine European universities, one regulatory agency, one non-profit research organization, four SMEs together with scientists from twelve pharmaceutical companies. The OrBiTo project will address key gaps in our knowledge of gastrointestinal (GI) drug absorption and deliver a framework for rational application of predictive biopharmaceutics tools for oral drug delivery. This will be achieved through novel prospective investigations to define new methodologies as well as refinement of existing tools. Extensive validation of novel and existing biopharm…
IMI – Oral biopharmaceutics tools project – Evaluation of bottom-up PBPK prediction success part 3: Identifying gaps in system parameters by analysin…
2016
Three Physiologically Based Pharmacokinetic software packages (GI-Sim, Simcyp® Simulator, and GastroPlus™) were evaluated as part of the Innovative Medicine Initiative Oral Biopharmaceutics Tools project (OrBiTo) during a blinded “bottom-up” anticipation of human pharmacokinetics. After data analysis of the predicted vs. measured pharmacokinetics parameters, it was found that oral bioavailability (Foral) was underpredicted for compounds with low permeability, suggesting improper estimates of intestinal surface area, colonic absorption and/or lack of intestinal transporter information. Foral was also underpredicted for acidic compounds, suggesting overestimation of impact of ionisation on pe…
Predicting Pharmacokinetics of Multisource Acyclovir Oral Products Through Physiologically Based Biopharmaceutics Modeling.
2021
Abstract Highly variable disposition after oral ingestion of acyclovir has been reported, although little is known regarding the underlying mechanisms. Different studies using the same reference product (Zovirax ®) showed that Cmax and AUC were respectively 44 and 35% lower in Saudi Arabians than Europeans, consistent with higher frequencies of reduced-activity polymorphs of the organic cation transporter (OCT1) in Europeans. In this study, the contribution of physiology (i.e., OCT1 activity) to the oral disposition of acyclovir immediate release (IR) tablets was hypothesized to be greater than dissolution. The potential role of OCT1 was studied in a validated physiologically-based biopharm…
Current Evidence, Challenges, and Opportunities of Physiologically Based Pharmacokinetic Models of Atorvastatin for Decision Making
2021
Atorvastatin (ATS) is the gold-standard treatment worldwide for the management of hypercholesterolemia and prevention of cardiovascular diseases associated with dyslipidemia. Physiologically based pharmacokinetic (PBPK) models have been positioned as a valuable tool for the characterization of complex pharmacokinetic (PK) processes and its extrapolation in special sub-groups of the population, leading to regulatory recognition. Several PBPK models of ATS have been published in the recent years, addressing different aspects of the PK properties of ATS. Therefore, the aims of this review are (i) to summarize the physicochemical and pharmacokinetic characteristics involved in the time-course o…
Physiologically-Based Pharmacokinetic/Pharmacodynamic Model of MBQ-167 to Predict Tumor Growth Inhibition in Mice
2020
MBQ-167 is a dual inhibitor of the Rho GTPases Rac and Cdc42 that has shown promising results as an anti-cancer therapeutic at the preclinical stage. This drug has been tested in vitro and in vivo in metastatic breast cancer mouse models. The aim of this study is to develop a physiologically based pharmacokinetic/pharmacodynamic (PBPK-PD) model of MBQ-167 to predict tumor growth inhibition following intraperitoneal (IP) administration in mice bearing Triple Negative and HER2+ mammary tumors. PBPK and Simeoni tumor growth inhibition (TGI) models were developed using the Simcyp V19 Animal Simulator. Our developed PBPK framework adequately describes the time course of MBQ-167 in each of the mo…