Evaluation of an integrated in vitro–in silico PBPK (physiologically based pharmacokinetic) model to provide estimates of human bioavailability

Towards Prediction of In Vivo Intestinal Absorption Using a 96-Well Caco-2 Assay

“…Mandagere et al 16 presented a graphical model using Spotfire software for estimating bioavailability from in vitro permeability and metabolic stability data. Beyond simple visualizations, physiologically based pharmacokinetic (PBPK) models can integrate several compound properties and additional in vitro data, such as protein binding, [17][18][19][20] for properly interpreting ADME profiling data and optimizing bioavailability. In the discussion, we presented the reality of integrating permeability assessment from this validated Caco-2 model with available solubility and metabolic stability data for pharmacokinetic (PK) decision making at Novartis.…”

Dynamic Dissolution Testing To Establish In Vitro/In Vivo Correlations for Montelukast Sodium, a Poorly Soluble Drug

“…Physiologically based models for the prediction of the gastrointestinal transit and absorption of drugs in humans have received much attention recently (11)(12)(13)(14). GastroPlus™ (version.…”

In Silico Prediction of Human Plasma Protein Binding Using Hologram QSAR

“…The absorption characteristic of an orally-administered drug is typically related to the drug's permeability -its ability to cross intestinal cell barriers before being distributed throughout the body toward the site of action. Plasma protein binding (PPB) plays a crucial role in drug design, determining the fraction of bioavailable free drug distributed through the various tissues [7]. A number of acidic drugs have high affinity for sites on blood proteins, particularly albumin, whereas the main binding protein for many basic drugs is alpha-1-acid glycoprotein (AGP) [8].…”