Allosteric inhibition of topoisomerase I by pinostrobin: Molecular docking, spectroscopic and topoisomerase I activity studies

Allosteric inhibition of topoisomerase I by pinostrobin: Molecular docking, spectroscopic and topoisomerase I activity studies

Authors: Jadaun K, Subbarao N, Dixit A
Publication: J Photochem Photobiol B
Keywords: DNA binding, molecular docking, topoisomerase I inhibitor
Software: MedChem Designer™

Cancer, the second major cause of mortality trailing the cardiovascular diseases, is a multifactorial heterogeneous disease and growing public health problem worldwide.

Report from EMA Workshop on Qualification and Reporting of Physiologically‐based Pharmacokinetic (PBPK) Modelling and Simulation

Report from EMA Workshop on Qualification and Reporting of Physiologically‐based Pharmacokinetic (PBPK) Modelling and Simulation

Authors: Zhao P
Publication: CPT Pharmacometrics Syst Pharmacol
Keywords: biological models, computer simulation, humans, PBPK modeling, pharmaceutical preparations, pharmacokinetic
Software: GastroPlus®

On Nov 21, 2016, the European Medicines Agency (EMA) hosted a workshop to discuss its draft guideline on qualification and reporting of physiologically based pharmacokinetic (PBPK) analysis.

The role of quantitative systems pharmacology modeling in the prediction and explanation of idiosyncratic drug-induced liver injury

The role of quantitative systems pharmacology modeling in the prediction and explanation of idiosyncratic drug-induced liver injury

Authors: Woodhead JL, Watkins PB, Howell BA, Siler SQ, Shoda LKM
Publication: Drug Metab Pharmacokinet
Keywords: adaptive immune system, computer modeling, idiosyncratic DILI, liver injury, quantitative systems pharmacology
Software: DILIsym®
Division: Quantitative Systems Pharmacology (QSP)

Idiosyncratic drug-induced liver injury (iDILI) is a serious concern in drug development.

Virtual population pharmacokinetic using physiologically based pharmacokinetic model for evaluating bioequivalence of oral lacidipine formulations in dogs

Virtual population pharmacokinetic using physiologically based pharmacokinetic model for evaluating bioequivalence of oral lacidipine formulations in dogs

Authors: Yang B, Wu C, Ji B, Wu M, He Z, Shang L, Sun J
Publication: Asian J Pharm Sci
Keywords: amorphous solid dispersions, bioequivalence, lacidipine, physiologically based pharmacokinetic modeling, virtual population pharmacokinetic

The aim of the present study was to investigate virtual population pharmacokinetic using physiologically based pharmacokinetic (PBPK) model for evaluating bioequivalence of oral lacidipine formulations in dogs.

Discovery of N-(pyridin-4-yl)-1,5-naphthyridin-2-amines as potential tau pathology PET tracers for Alzheimer’s Disease.

Discovery of N-(pyridin-4-yl)-1,5-naphthyridin-2-amines as potential tau pathology PET tracers for Alzheimer’s Disease.

Authors: Rombouts FJR, Andrés JI, Ariza M, Alonso JM, Austin N, Bottelbergs A, Chen L, Chupakhin V, Cleiren E, Fierens K, Fontana A, Langlois X, Leenaerts JE, Mariën J, Martinez Lamenca C, Salter R, Schmidt ME, Te Riele P, Wintmolders C, Trabanco AA, Zhang W, Macdonald GJ, Moechars D
Publication: J Med Chem
Keywords: alzheimer's disease, medicinal chemistry, pharmacokinetic
Software: ADMET Predictor®

A mini-HTS on 4000 compounds selected using 2D fragment-based similarity and 3D pharmacophoric and shape similarity to known selective tau aggregate binders identified...

IMI – oral biopharmaceutics tools project – evaluation of bottom-up PBPK prediction success part 1: Characterisation of the OrBiTo database of compounds

IMI – oral biopharmaceutics tools project – evaluation of bottom-up PBPK prediction success part 1: Characterisation of the OrBiTo database of compounds

Authors: Margolskee A, Darwich AS, Pepin X, Pathak SM, Bolger MB, Aarons L, Rostami-Hodjegan A, Angstenberger J, Graf F, Laplanche L, Müller T, Carlert S, Daga PR, Murphy D, Tannergren C, Yasin M, Greschat-Schade S, Mück W, Muenster U, van der Mey D, Frank KJ, Lloyd R, Adriaenssen L, Bevernage J, De Zwart L, Swerts D, Tistaert C, Van Den Bergh A, Van Peer A, Bennett J, McAllister M, Wong M, Zane P, Ollier C, Vicat P, Kolhmann M, Marker A, Brun P, Mazuir F, Beilles S, Venczel M, Boulenc X, Loos P, Lennernäs H, Abrahamsson B
Publication: Eur J Pharm Sci
Keywords: absorption biopharmaceutics, drug database, modelling and simulation (M&S), oral bioavailability (F(oral)), physiologically based pharmacokinetics (PBPK)

Predicting oral bioavailability (Foral) is of importance for estimating systemic exposure of orally administered drugs.

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

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

Authors: Darwich AS, Margolskee A, Pepin X, Aarons L, Galetin A, Rostami-Hodjegan A, Carlert S, Hammarberg M, Hilgendorf C, Johansson P, Karlsson E, Murphy D, Tannergren C, Thörn H, Yasin M, Mazuir F, Nicolas O, Ramusovic S, Xu C, Pathak SM, Korjamo T, Laru J, Malkki J, Pappinen S, Tuunainen J, Dressman J, Hansmann S, Kostewicz ES, He H, Heimbach T, Wu F, Hoft C, Pang Y, Bolger MB, Huehn E, Lukacova V, Mullin JM, Szeto KX, Costales C, Lin J, McAllister M, Modi S, Rotter C, Varma M, Wong M, Mitra A, Bevernage J, Van Peer A, Lloyd R, Shardlow C, Langguth P, Mishenzon I, Nguyen MA, Brown J, Lennernäs H, Abrahamsson B
Publication: Eur J Pharm Sci
Keywords: absorption, biopharmaceutics, drug database, modelling and simulation (M&S), oral bioavailability (F(oral)), Physiologically based pharmacokinetic (PBPK) modeling
Software: GastroPlus®

Three Physiologically Based Pharmacokinetic software packages (GI-Sim, Simcyp® Simulator, and GastroPlus™) were evaluated as part of the Innovative Medicine Initiative Oral Biopharmaceutics Tools...

Prediction of pharmacokinetics and drug-drug interaction potential using physiologically based pharmacokinetic (PBPK) modeling approach: A case study of caffeine and ciprofloxacin

Prediction of pharmacokinetics and drug-drug interaction potential using physiologically based pharmacokinetic (PBPK) modeling approach: A case study of caffeine and ciprofloxacin

Authors: Park MH, Shin SH, Lee GH, Yu B, Shin YG
Publication: Korean J Physiol Pharmacol
Keywords: caffeine, ciprofloxacin, drug-drug interactions (DDIs), physiologically based pharmacokinetics
Software: ADMET Predictor®, GastroPlus®

Over the last decade, physiologically based pharmacokinetics (PBPK) application has been extended significantly not only to predicting preclinical/human PK but also to evaluating the drug-drug interaction...

IMI – Oral biopharmaceutics tools project – Evaluation of bottom-up PBPK prediction success part 2: An introduction to the simulation exercise and overview of results

IMI – Oral biopharmaceutics tools project – Evaluation of bottom-up PBPK prediction success part 2: An introduction to the simulation exercise and overview of results

Authors: Margolskee A, Darwich AS, Pepin X, Aarons L, Galetin A, Rostami-Hodjegan A, Carlert S, Hammarberg M, Hilgendorf C, Johansson P, Karlsson E, Murphy D, Tannergren C, Thörn H, Yasin M, Mazuir F, Nicolas O, Ramusovic S, Xu C, Pathak SM, Korjamo T, Laru J, Malkki J, Pappinen S, Tuunainen J, Dressman J, Hansmann S, Kostewicz ES, He H, Heimbach T, Wu F, Hoft C, Laplanche L, Pang Y, Bolger MB, Huehn E, Lukacova V, Mullin JM, Costales C, Lin J, McAllister M, Modi S, Rotter C, Varma M, Wong M, Mitra A, Bevernage J, Biewenga J, Van Peer A, Lloyd R, Shardlow C, Langguth P, Mishenzon I, Nguyen MA, Brown J, Lennernäs H, Abrahamsson B
Publication: Eur J Pharm Sci
Keywords: absorption, biopharmaceutics, drug database, modelling and simulation (M&S), oral bioavailability (F(oral)), physiologically based pharmacokinetics (PBPK)
Software: GastroPlus®

Orally administered drugs are subject to a number of barriers impacting bioavailability (Foral), causing challenges during drug and formulation development.

Application of a Mechanistic Model to Evaluate Putative Mechanisms of Tolvaptan Drug-Induced Liver Injury and Identify Patient Susceptibility Factors.

Application of a Mechanistic Model to Evaluate Putative Mechanisms of Tolvaptan Drug-Induced Liver Injury and Identify Patient Susceptibility Factors.

Authors: Woodhead JL, Brock WJ, Roth SE, Shoaf SE, Brouwer KL, Church R, Grammatopoulos TN, Stiles L, Siler SQ, Howell BA, Mosedale M, Watkins PB, Shoda LKM
Publication: Toxicol Sci
Keywords: ADPKD, DILI, quantitative systems pharmacology modeling, tolvaptan
Software: DILIsym®
Division: Quantitative Systems Pharmacology (QSP)

Tolvaptan is a selective vasopressin V2 receptor antagonist, approved in several countries for the treatment of hyponatremia and autosomal dominant polycystic kidney disease (ADPKD).

In vitro and in silico characterisation of Tacrolimus released under biorelevant conditions

In vitro and in silico characterisation of Tacrolimus released under biorelevant conditions

Authors: Mercuri A, Wu S, Stranzinger S, Mohr S, Salar-Behzadi S, Bresciani M, Fröhlich E
Publication: Int J Pharm
Keywords: biorelevant dissolution, permeability, PK modelling, solubility, tacrolimus

This work aims to better understand the in vivo behaviour of modified release (MR) formulations (Envarsus® tablets and Advagraf® capsules) using in vitro properties of tacrolimus and in silico simulations.