In Silico Prediction of Major Drug Clearance Pathways by Support Vector Machines with Feature-Selected Descriptors

In Silico Prediction of Major Drug Clearance Pathways by Support Vector Machines with Feature-Selected Descriptors

Authors: Toshimoto K, Wakayama N, Kusama M, Maeda K, Sugiyama Y, Akiyama Y
Publication: Drug Metab Dispos
Keywords: computer simulation, in silico, pharmacokinetics, support vector machine
Software: ADMET Predictor®

We have previously established an in silico classification method ("CPathPred") to predict the major clearance pathways of drugs based on an empirical decision with only four physicochemical...

Dissolution testing combined with computer simulation technology to evaluate the bioequivalence of domestic amoxicillin capsule

Dissolution testing combined with computer simulation technology to evaluate the bioequivalence of domestic amoxicillin capsule

Authors: Pan RX, Gao Y, Chen WL, Li YL, Hu CQ
Publication: Yao Xue Xue Bao
Keywords: Amoxicillin, computer simulation, equivalency, gastrointestinal tract (GIT), humans, pharmacokinetics, solubility, therapeutic
Software: GastroPlus®

Re-evaluation of bioequivalence of generic drugs is one of the key research focus currently. As a means to ensure consistency of the therapeutic effectiveness of drug products, clinical bioequivalence...

Intestinal transport of TRH analogs through PepT1: the role of in silico and in vitro modeling

Intestinal transport of TRH analogs through PepT1: the role of in silico and in vitro modeling

Authors: Bagul P, Khomane KS, Kesharwani SS, Pragyan P, Nandekar PP, Meena CL, Bansal AK, Jain R, Tikoo K, Sangamwar AT
Publication: J Mol Recognit
Keywords: Caco-2 cells, computer simulation, molecular docking simulation, permeability, thyrotropin releasing hormone (TRH)
Software: GastroPlus®

The present study involves molecular docking, molecular dynamics (MD) simulation studies, and Caco-2 cell monolayer permeability assay to investigate the effect of structural modifications on...

Enhanced Solubility and Oral Bioavailability of y-Tocotrienol Using a Self-Emulsifying Drug Delivery System (SEDDS)

Enhanced Solubility and Oral Bioavailability of y-Tocotrienol Using a Self-Emulsifying Drug Delivery System (SEDDS)

Authors: Alqahtani S, Alayoubi A, Nazzal S, Sylvester PW, Kaddoumi A
Publication: Lipids
Keywords: animals, antineoplastic agents, area under curve, biological availability, Caco-2 cells, chromans, drug delivery systems, emulsifying agents, humans, lipolysis, pharmacokinetics, rats, solubility, vitamin E
Software: GastroPlus®

The aim of this study was to evaluate the in vitro and in vivo performance of γ-tocotrienol (γ-T3) incorporated in a self-emulsifying drugdelivery system (SEDDS)...

Design of a General-Purpose European Compound Screening Library for EU-OPENSCREEN

Design of a General-Purpose European Compound Screening Library for EU-OPENSCREEN

Authors: Horvath D, Lisurek M, Rupp B, Kühne R, Specker E, von Kries J, Rognan D, Andersson CD, Almqvist F, Elofsson M, Enqvist PA, Gustavsson AL, Remez N, Mestres J, Marcou G, Varnek A, Hibert M, Quintana J, Frank R
Publication: ChemMedChem
Keywords: chemical space mapping, commercial compound selection, EU-OPENSCREEN, library design, molecular diversity, self-organizing maps
Software: MedChem Studio™

This work describes a collaborative effort to define and apply a protocol for the rational selection of a general-purpose screening library, to be used by the screening platforms affiliated with the EU-OPENSCREEN initiative.

Predicting when Biliary Excretion of Parent Drug is a Major Route of Elimination in Humans

Predicting when Biliary Excretion of Parent Drug is a Major Route of Elimination in Humans

Authors: Hosey CM, Broccatelli F, Benet LZ
Publication: AAPS J
Keywords: biological models, chemical models, hepatobiliary elimination, humans, hydrophobic and hydrophilic Interactions, least-squares analysis, linear models, logistic models, membrane transport proteins, metabolism, molecular weight, oral administration, particle size, permeability, pharmaceutical preparations, pharmacokinetics, reproducibility of results
Software: ADMET Predictor®

Biliary excretion is an important route of elimination for many drugs, yet measuring the extent of biliary elimination is difficult, invasive, and variable. 

Mechanistic Modeling Reveals the Critical Knowledge Gaps in Bile Acid-Mediated DILI

Mechanistic Modeling Reveals the Critical Knowledge Gaps in Bile Acid-Mediated DILI

Authors: Woodhead JL, Yang K, Brouwer KL, Siler SQ, Stahl SH, Ambroso JL, Baker D, Watkins PB, Howell BA
Publication: CPT Pharmacometrics Syst Pharmacol
Keywords: bile acid (BA) homeostasis, drug-induced liver injury, humans, in vivo, liver concentrations, rats
Software: DILIsym®
Division: Quantitative Systems Pharmacology (QSP)

Bile salt export pump (BSEP) inhibition has been proposed to be an important mechanism for drug-induced liver injury (DILI). 

Physiologically based pharmacokinetic modeling for assessing the clinical drug-drug interaction of alisporivir

Physiologically based pharmacokinetic modeling for assessing the clinical drug-drug interaction of alisporivir

Authors: Xia B, Barve A, Heimbach T, Zhang T, Gu H, Wang L, Alexander N, Hanna I, Ke J, Mangold JB, He H, Sunkara G
Publication: Eur J Pharm Sci
Keywords: alisporivir, clearance, CYP3A4, drug-drug interactions (DDIs), Physiologically based pharmacokinetic (PBPK) modeling, time-dependent inhibition
Software: ADMET Predictor®

Alisporivir is a novel cyclophilin-binding molecule with potent anti-hepatitis C virus (HCV) activity. In vitro data from human liver microsomes suggest that alisporivir is a substrate and a time-dependent inhibitor (TDI) of CYP3A4.

Freezing the Bioactive Conformation to Boost Potency: The Identification of BAY 85-8501, a Selective and Potent Inhibitor of Human Neutrophil Elastase for Pulmonary Diseases

Freezing the Bioactive Conformation to Boost Potency: The Identification of BAY 85-8501, a Selective and Potent Inhibitor of Human Neutrophil Elastase for Pulmonary Diseases

Authors: von Nussbaum F, Li VM, Allerheiligen S, Anlauf S, Bärfacker L, Bechem M, Delbeck M, Fitzgerald MF, Gerisch M, Gielen-Haertwig H, Haning H, Karthaus D, Lang D, Lustig K, Meibom D, Mittendorf J, Rosentreter U, Schäfer M, Schäfer S, Schamberger J, Telan LA, Tersteegen A
Publication: ChemMedChem
Keywords: biginelli reaction, biological activity, elastase inhibitors, inflammatory diseases, proteases, pulmonary diseases, pyrimidinones
Software: ADMET Predictor®

Human neutrophil elastase (HNE) is a key protease for matrix degradation. High HNE activity is observed in inflammatory diseases.

Translational PK/PD modeling for cardiovascular safety assessment of drug candidates: Methods and examples in drug development

Translational PK/PD modeling for cardiovascular safety assessment of drug candidates: Methods and examples in drug development

Authors: Caruso A, Frances N, Meille C, Greiter-Wilke A, Hillebrecht A, Lavé T
Publication: J Pharmacol Toxicol Methods
Keywords: cardiovascular safety pharmacology, nonlinear mixed effects modeling, PK/PD modeling, telemetry studies, translation to human
Software: GastroPlus®

Cardiovascular toxicity is a significant cause of candidate failure in drug development. Pharmacokinetic/pharmacodynamic (PK/PD) modeling may reduce attrition by improving the understanding...