0000000000466859
AUTHOR
Michael B. Bolger
showing 6 related works from this author
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 4: Prediction accuracy and software comparisons with…
2020
Oral drug absorption is a complex process depending on many factors, including the physicochemical properties of the drug, formulation characteristics and their interplay with gastrointestinal physiology and biology. Physiological-based pharmacokinetic (PBPK) models integrate all available information on gastro-intestinal system with drug and formulation data to predict oral drug absorption. The latter together with in vitro-in vivo extrapolation and other preclinical data on drug disposition can be used to predict plasma concentration-time profiles in silico. Despite recent successes of PBPK in many areas of drug development, an improvement in their utility for evaluating oral absorption i…
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…
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 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…
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…