0000000000388368
AUTHOR
Viera Lukacova
In vivo methods for drug absorption - comparative physiologies, model selection, correlations with in vitro methods (IVIVC), and applications for formulation/API/excipient characterization including food effects.
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 3: Identifying gaps in system parameters by analysing In Silico performance across different compound classes
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…
IMI – Oral biopharmaceutics tools project – Evaluation of bottom-up PBPK prediction success part 2: An introduction to the simulation exercise and overview of results
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…