Structure-activity relationship read-across and transcriptomics for branched carboxylic acids

Structure-activity relationship read-across and transcriptomics for branched carboxylic acids

Authors: Wu S, Ellison C, Naciff J, Karb M, Obringer C, Yan G, Shan Y, Smith A, Wang X, Daston GP
Publication: Toxicol Sci
Keywords: admet predictor, chemicals, cosmetics, gastroplus, IVIVE, pbk, PBPK modeling, physiologically based pharmacokinetics, read-across, risk assessment
Software: GastroPlus®

The purpose of this study was to use chemical similarity evaluations, transcriptional profiling, in vitro toxicokinetic data, and physiologically based pharmacokinetic (PBPK)...

In-Depth Analysis of Physiologically Based Pharmacokinetic (PBPK) Modeling Utilization in Different Application Fields Using Text Mining Tools

In-Depth Analysis of Physiologically Based Pharmacokinetic (PBPK) Modeling Utilization in Different Application Fields Using Text Mining Tools

Authors: Krstevska A, Duriš J, Ibric S, Cvijić S
Publication: Pharmaceutics
Keywords: Modeling and simulations, pbbm, PBBM modeling, PBPK modeling, text mining, topic modeling

In the past decade, only a small number of papers have elaborated on the application of physiologically based pharmacokinetic (PBPK) modeling across different areas.

Pharmacokinetic Basis for Using Saliva Matrine Concentrations as a Clinical Compliance Monitoring in Antitumor B Chemoprevention Trials in Humans

Pharmacokinetic Basis for Using Saliva Matrine Concentrations as a Clinical Compliance Monitoring in Antitumor B Chemoprevention Trials in Humans

Authors: Bui D, McWilliams LA, Wu L, Zhou H, Wong SJ, You M, Chow DS, Singh R, Hu M
Publication: Cancers (Basel)
Keywords: ACAT, gastroplus, mechanistic absorption, Oncology, pbbm, PBPK modeling, physiologically based pharmacokinetics

This study reports the first clinical evidence of significantly high secretion of matrine in a multi-component botanical (Antitumor B, ATB) into human saliva from the systemic...

Prediction of Drug Synergism between Peptides and Antineoplastic Drugs Paclitaxel, 5-Fluorouracil, and Doxorubicin Using In Silico Approaches

Prediction of Drug Synergism between Peptides and Antineoplastic Drugs Paclitaxel, 5-Fluorouracil, and Doxorubicin Using In Silico Approaches

Authors: Vale N, Pereira M, Santos J, Moura C, Marques L, Duarte D
Publication: Int J Mol Sciences
Keywords: ACAT, admet predictor, dose optimization, gastroplus, mechanistic absorption, PBPK modeling, physiologically based pharmacokinetics
Software: GastroPlus®

Chemotherapy is the main treatment for most early-stage cancers; nevertheless, its efficacy is usually limited by drug resistance, toxicity, and tumor heterogeneity.

Non-specific binding of compounds in in vitro metabolism assays: a comparison of microsomal and hepatocyte binding in different species and an assessment of the accuracy of prediction models

Non-specific binding of compounds in in vitro metabolism assays: a comparison of microsomal and hepatocyte binding in different species and an assessment of the accuracy of prediction models

Authors: Gardner I, Xu M, Han C, Wang Y, Jiao X, Jamei M, Southall R, Turner DB, Musther H, Jones B, Taylor S
Publication: Xenobiotica
Keywords: hepatocytes, in vitro assays, In vitro metabolism
Division: PBPK

Non-specific binding in in vitro metabolism systems leads to an underestimation of the true intrinsic metabolic clearance of compounds being studied.

Effect of starch, cellulose and povidone based superdisintegrants in a QbD-based approach for the development and optimization of Nitazoxanide orodispersible tablets: Physicochemical characterization, compaction behavior and in-silico PBPK modeling of its active metabolite Tizoxanide

Effect of starch, cellulose and povidone based superdisintegrants in a QbD-based approach for the development and optimization of Nitazoxanide orodispersible tablets: Physicochemical characterization, compaction behavior and in-silico PBPK modeling of its active metabolite Tizoxanide

Authors: Irshad A, Yousuf RI, Shoaib MH, Qazi F, Saleem MT, Siddiqui F, Ahmed FR, Rehman R, Jabeen S, Farooqi S, Khan MZ, Masood R
Publication: J Drug Deliv Sci Technol
Keywords: ACAT, biopharmaceutics, gastroplus, mechanistic absorption, metabolite tracking, pbbm, PBPK modeling, physiologically based pharmacokinetics, Quality by design
Software: GastroPlus®

The objective of the study was to develop a QbD based orodispersible Nitazoxanide 200 mg tablets its in-silico PBPK modeling. The central composite design was applied...

Model-Informed drug development of gastroretentive release systems for sildenafil citrate

Model-Informed drug development of gastroretentive release systems for sildenafil citrate

Authors: Pinheiro de Souza F, Sonego Zimmermann E, Tafet Carminato Silva R, Novaes Borges L, Villa Nova M, Miriam de Souza Lima M, Diniz A
Publication: Eur J Pharm Biopharm
Keywords: ACAT, bioequivalence, biopharmaceutics, gastroplus, mechanistic absorption, pbbm, PBPK modeling, physiologically based pharmacokinetics, vbe
Software: GastroPlus®

Gastroretentive drug delivery systems (GRDDS) are modified-release dosage forms designed to prolong their residence time in the upper gastrointestinal tract...

Using mechanistic models to support development of complex generic drug products: European Medicines Agency perspective

Using mechanistic models to support development of complex generic drug products: European Medicines Agency perspective

Authors: Manolis E, Garcia-Arieta A, Lindahl A, Kotzagiorgis E, Limberg J, Holte O, Paixao P, Versantvoort C, Tshinanu FM, Blake K, Van Den Heuvel M
Publication: CPT Pharmacometrics Syst Pharmacol
Keywords: bioequivalence (BE), European Medicines Agency (EMA), model‐informed drug development, PBPK modeling

Model‐informed drug development (MIDD) approaches receive wide regulatory acceptance in the European Medicines Agency (EMA) to support new drug development.

Greater efficacy predicted for FGR1/beta-klotho receptor agonists that achieve 60% or greater increases in serum adiponectin

Greater efficacy predicted for FGR1/beta-klotho receptor agonists that achieve 60% or greater increases in serum adiponectin

Authors: Lakhani VV, Tirucherai G, Generaux GT, Siler SQ
Conference: AASLD
Keywords: adiponectin, efruxifermin, FGFR1, fibrosis, NASH, pegbelfermin, quantitative systems pharmacology (QSP)
Software: NAFLDsym®
Division: Quantitative Systems Pharmacology (QSP)

The FGFR1/beta-klotho receptor (FGFR1/KLB) in adipose has been demonstrated to be a...

Reduction of daily moderate alcohol intake predicted to decrease fibrosis stage in patients with non-alcholic steatohepatitis

Reduction of daily moderate alcohol intake predicted to decrease fibrosis stage in patients with non-alcholic steatohepatitis

Authors: Battista C, Beaudoin J, Yang K, Siler SQ
Conference: AASLD
Keywords: fibrosis, gastroplus, lipogenesis, NAFLDsym, NASH, quantitative systems pharmacology (QSP)
Software: GastroPlus®, NAFLDsym®
Division: Quantitative Systems Pharmacology (QSP)

Several recently completed clinical trials in NASH patients have included fibrosis stage reductions in...

Impact of chemical structure on the in vitro hydrolysis of fatty esters of 2-ethylhexanoic acid or 2-ethylhexanol and extrapolation to the in vivo situation

Impact of chemical structure on the in vitro hydrolysis of fatty esters of 2-ethylhexanoic acid or 2-ethylhexanol and extrapolation to the in vivo situation

Authors: Obringer C, Lester C, Karb M, Smith A, Ellison CA
Publication: Regul Toxicol Pharmacol
Keywords: admet predictor, chemicals, cosmetics, gastroplus, IVIVE, pbk, PBPK modeling, physiologically based pharmacokinetics, risk assessment
Software: GastroPlus®

Fatty esters of 2-ethylhexanoic acid (EHA) and 2-ethylhexanol (EH) are commonly used in cosmetics. Human liver and skin S9 and human plasma were used to determine the...

Mathematical Representation of Drug-Induced Crystal Nephropathy Using a Quantitative Systems Toxicology Approach

Mathematical Representation of Drug-Induced Crystal Nephropathy Using a Quantitative Systems Toxicology Approach

Authors: Tallapaka SB, Bhargava P, Koirala B, Woodhead JL
Conference: American Society of Nephrology (ASN) Kidney Week
Keywords: Acute kidney injury (AKI), crystal nephropathy, gastroplus, Indinavir, kidney, Quantitative Systems Toxicology (QST), RENAsym
Software: GastroPlus®, RENAsym®
Division: Quantitative Systems Pharmacology (QSP)

Drugs may cause crystal nephropathy by precipitating within kidney tubules or inducing...

Formulation development and optimization of taste-masked azithromycin oral suspension with ion exchange resins: Bioanalytical method development and validation, in vivo bioequivalence study, and in-silico PBPK modeling for the paediatric population

Formulation development and optimization of taste-masked azithromycin oral suspension with ion exchange resins: Bioanalytical method development and validation, in vivo bioequivalence study, and in-silico PBPK modeling for the paediatric population

Authors: Siddiqui F, Shoaib MH, Ahmed FR, Qazi F, Yousuf RI, Usmani MT, Saleem MT, Ahmed K
Publication: J Drug Deliv Sci Technol
Keywords: ACAT, biopharmaceutics, children, gastroplus, mechanistic absorption, pbbm, PBPK modeling, pediatrics, physiologically based pharmacokinetics
Software: GastroPlus®

The study is based on preparing taste-masked oral suspension of azithromycin using ion exchange resins Kyron T135 and Doshion-P542 AB. The complexation...

Mathematical Modeling of Renal Sodium, Potassium, and Glucose Dynamics in Diabetic and Non-Diabetic Simulated Populations

Mathematical Modeling of Renal Sodium, Potassium, and Glucose Dynamics in Diabetic and Non-Diabetic Simulated Populations

Authors: Battista C, Cheng L, Hamzavi N, Bhargava P, Siler SQ
Conference: ACoP
Keywords: absorption, diuretic, glucose, potassium, quantitative systems pharmacology (QSP), quantitative systems pharmacology (QSP) model, Type 2 diabetes
Division: Quantitative Systems Pharmacology (QSP)

Type 2 diabetic (T2D) patients often exhibit reduced systolic and diastolic functions, which can place them at...