Danoprevir, a potent, selective inhibitor of HCV NS3/4A protease, has a short half-life in humans. Therefore, the feasibility of a controlled release (CR) formulation to allow less frequent dosing...
Simulation of human intravenous and oral pharmacokinetics of 21 diverse compounds using physiologically based pharmacokinetic modelling
The importance of predicting human pharmacokinetics during compound selection has been recognized in the pharmaceutical industry. To this end there are many different approaches that are applied.
A Model of Threshold Behavior Reveals Rescue Mechanisms of Bystander Proteins in Conformational Diseases
Conformational diseases result from the failure of a specific protein to fold into its correct functional state. The misfolded proteins can lead to the toxic aggregation of proteins.
Black tea improves attention and self-reported alertness
Tea has previously been demonstrated to better help sustain alertness throughout the day in open-label studies.
Utility of Physiologically Based Absorption Modeling in Implementing Quality by Design in Drug Development
To implement Quality by Design (QbD) in drug development, scientists need tools that link drug products properties to in vivo performance
In Vitro-In Vivo Correlation for Gliclazide Immediate-Release Tablets Based on Mechanistic Absorption Simulation.
The aim of this study was to develop a drug-specific absorption model for gliclazide (GLK) using mechanistic gastrointestinal simulation technology (GIST) implemented...
Prediction of Oral Pharmacokinetics of cMet Kinase Inhibitors in Humans: Physiologically Based Pharmacokinetic Model versus Traditional One Compartment Model.
The objective of this study was to assess the physiologically based pharmacokinetic (PBPK) model for predicting plasma concentration-time profiles...
Use of structure-activity landscape index curves and curve integrals to evaluate the performance of multiple machine learning prediction models
Standard approaches to address the performance of predictive models that used common statistical measurements for the entire data set provide an overview of...
Pharmacokinetics of dietary cancer chemopreventive compound dibenzoylmethane in rats and the impact of nanoemulsion and genetic knockout of Nrf2 on its disposition
The pharmacokinetic disposition of a dietary cancer chemopreventive compound dibenzoylmethane (DBM) was studied in male Sprague-Dawley rats after intravenous...
Trends in kinase selectivity: insights for target class-focused library screening
A kinome-wide selectivity screen of >20000 compounds with a rich representation of many structural classes has been completed.
Bendamustine pharmacokinetic profile and exposure-response relationships in patients with indolent non-Hodgkin’s lymphoma
The pharmacokinetic profiles of bendamustine and active metabolites were defined in patients with rituximab-refractory, relapsed indolent B-cell non-Hodgkin's lymphoma, and supported understanding of exposure-response relationships for efficacy and safety.
Dissolution modeling of bead formulations and predictions of bioequivalence for a highly soluble, highly permeable drug
The objective of this study was to assess the impact of observed in vitro dissolution rate differences on in vivo pharmacokinetics for two enteric-coated bead formulations...
The biowaivers extension for BCS Class III drugs: the effect of dissolution rate on on the bioequivalence of BCS Class III IR drugs predicted by computer simulation
The Biopharmaceutical Classification System (BCS) guidance issued by the FDA allows waivers for in vivo bioavailability and bioequivalence studies for immediate-release...
In Silico Classification of Major Clearance Pathways of Drugs with Their Physiochemical Parameters
Predicting major clearance pathways of drugs is important in understanding their pharmacokinetic properties in clinical use, such as drug-drug interactions and genetic...
Plasma pharmacokinetics of two consecutive doses of ferumoxytol in healthy subjects
Intravenous (IV) iron is used to treat iron-deficiency anemia in patients with chronic kidney disease (CKD). Ferumoxytol is a novel iron formulation administered rapidly as two IV boluses of 510 mg each. In this placebo-controlled, double-blind...
Improving productivity with model-based drug development: an enterprise perspective
The productivity of the pharma enterprise has fallen, as evidenced by a decline in regulatory submissions and less commercial success.
A pH-Dilution Method for Estimation of Biorelevant Drug Solubility along the Gastrointestinal Tract: Application to Physiologically Based Pharmacokinetic Modeling
Physiologically based pharmacokinetic (PBPK) modeling tools have become an integral part of the modern drug discovery−development process.
Rationalizing the development of live attenuated virus vaccines
The design of vaccines against viral disease has evolved considerably over the past 50 years. Live attenuated viruses (LAVs)-those created by passaging a virus in cultured...
AR inhibitors identified by high-throughput microscopy detection of conformational change and subcellular localization
Signaling via the androgen receptor (AR) plays an important role in human health and disease. All currently available anti-androgens prevent ligand access to the receptor...
Quantitative Prediction of Regioselectivity Toward Cytochrome P450/3A4 Using Machine Learning Approaches
In the drug discovery process, it is important to know the properties of both drug candidates and their metabolites.