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.
Prediction of pharmacokinetic profile of valsartan in human based on in vitro uptake transport data
The aim of this study was to evaluate a strategy based on a physiologically based pharmacokinetic (PBPK) model for the prediction of PK profiles in human using in vitro...
Optimizing the Performance of In Silico ADMET General Models According to Local Requirements: MARS Approach. Solubility Estimations As Case Study
The quality of in vitro data used to build in silico absorption, distribution, metabolism, and toxicity (ADMET) models is, in many cases, inconsistent.
In Silico Prediction of Aqueous Solubility: The Solubility Challenge
The dissolution of a chemical into water is a process fundamental to both chemistry and biology. The persistence of a chemical within the environment and the effects of a chemical...
Exposure-response analyses of tigecycline tolerability in healthy subjects
Tigecycline exposure (area under the concentration-time curve [AUC((0-infinity))] and maximum serum concentration [C(max)]) and first occurrence of nausea and vomiting were evaluated in 136 healthy subjects after...