An Introduction to Mathematical Modeling in Drug Development using GastroPlus® and DILIsym®

An Introduction to Mathematical Modeling in Drug Development using GastroPlus® and DILIsym®

Authors: C Vallejo
Conference: SMB
Keywords: PBPK, physiological-based pharmacokinetic (PBPK), qsp, QSP (quantitative systems pharmacology) modeling software, QST, Quantitative Systems Toxicology (QST)
Software: DILIsym®, GastroPlus®
Division: PBPK, Quantitative Systems Pharmacology (QSP)

Introduction to drug development
Introduction to PBPK modeling
Introduction to QSP/QST modeling

Halloysite nanotubes-cellulose ether based biocomposite matrix, a potential sustained release system for BCS class I drug verapamil hydrochloride: Compression characterization, in-vitro release kinetics, and in-vivo mechanistic physiologically based pharmacokinetic modeling studies

Halloysite nanotubes-cellulose ether based biocomposite matrix, a potential sustained release system for BCS class I drug verapamil hydrochloride: Compression characterization, in-vitro release kinetics, and in-vivo mechanistic physiologically based pharmacokinetic modeling studies

Authors: Husain T, Shoaib MH, Ahmed FR, Yousuf RI, Siddiqui F, Saleem MT, Farooqi S, Jabeen S
Publication: International Journal of Molecular Sciences
Keywords: ACAT, drug release, formulation development, gastroplus, In silico PBPK modeling, in vitro dissolution, ivivr, mechanistic absorption, pbbm, PBPK modeling, physiologically based biopharmaceutics
Software: ADMET Predictor®, GastroPlus®

This study investigated the ability of natural nanotubular clay mineral (Halloysite) and cellulose ether based biocomposite matrix as a controlled release...

Microfluidic technology and simulation models in studying pharmacokinetics during pregnancy

Microfluidic technology and simulation models in studying pharmacokinetics during pregnancy

Authors: Kammala AK, Richardson LS, Radnaa E, Han A, Menon R
Publication: Front Pharmacol
Keywords: fetal exposure, gastroplus, PBPK modeling, physiologically based pharmacokinetics, placenta transfer, special populations
Software: GastroPlus®

Preterm birth rates and maternal and neonatal mortality remain concerning global health issues, necessitating improved strategies for testing therapeutic compounds during pregnancy.

ADME characterization and PBK model development of 3 highly protein-bound UV filters through topical application

ADME characterization and PBK model development of 3 highly protein-bound UV filters through topical application

Authors: Li H, Bunglawala F, Hewitt NJ, Pendlington R, Cubberley R, Nicol B, Spriggs S, Baltazar MT, Cable S, Dent M
Publication: Toxicol Sci
Keywords: chemicals, cosmetics, dermal absorption, gastroplus, IVIVE, machine learning, pbk modeling, PBPK modeling, physiologically based kinetic modeling, risk assessment, tcat
Software: GastroPlus®

Estimating human exposure in the safety assessment of chemicals is crucial. Physiologically based kinetic (PBK) models which combine information on exposure, physiology, and chemical properties...

AIDD, an interactive AI-driven drug design system that uses molecular evolution and mechanistic pharmacokinetic simulation to optimize multiple property objectives simultaneously

AIDD, an interactive AI-driven drug design system that uses molecular evolution and mechanistic pharmacokinetic simulation to optimize multiple property objectives simultaneously

Authors: Clark RD, Jones J, Lawless M, Miller D, Waldman M
Publication: Journal of Computer-Aided Molecular Design
Keywords: artificial intelligence, de novo drug design, generative chemistry technology, molecular modeling, QSAR, QSPR
Software: ADMET Predictor®, GastroPlus®
Division: PBPK

Computer-aided drug design has advanced rapidly in recent years, and multiple instances of in silico designed molecules advancing to the clinic have...

Researchers Use the Simulations Plus DILIsym® Platform to Predict Safety of Combined CBD and VPA Treatment

Researchers Use the Simulations Plus DILIsym® Platform to Predict Safety of Combined CBD and VPA Treatment

Keywords: cannabidiol (CBD), drug induced liver injury (DILI), Quantitative Systems Toxicology (QST), valproate (VPA)
Software: DILIsym®
Division: Quantitative Systems Pharmacology (QSP)

Elevated ALT levels during clinical trials led researchers to use quantitative systems toxicology (QST) software to better understand potential underlying mechanisms

Predicting bioequivalence and developing dissolution bioequivalence safe space in vitro for warfarin using a Physiologically-Based pharmacokinetic absorption model

Predicting bioequivalence and developing dissolution bioequivalence safe space in vitro for warfarin using a Physiologically-Based pharmacokinetic absorption model

Authors: Cheng ZZ, Hu X, Li YL, Zhang L
Publication: Eur J Pharm Biopharm
Keywords: gastroplus, mechanistic absorption, pbbm, PBPK modeling, physiologically based biopharmaceutics, safe space, vbe, virtual bioequivalence
Software: GastroPlus®

Bioequivalence (BE) studies support the approval and clinical use of both new and generic drug products.

Training the next generation of pharmacometric modelers: a multisector perspective

Training the next generation of pharmacometric modelers: a multisector perspective

Authors: Bonate P, Barrett JS, Ait-Oudhia S, Brundage R, Corrigan B, Duffull S, Gastonguay M, Karlsson MO, Kijima S, Krause A, Lovern M, Neely M, Ouellet D, Plan EL, Rao GG, Standing J, Wilkins J, Zhu H
Publication: J Pharmacokinet Pharmacodyn
Keywords: education, modeling and simulation, pharmacometrics

The current demand for pharmacometricians outmatches the supply provided by academic institutions and considerable investments are made to develop the competencies of these scientists on-the-job.

Physiologically based pharmacokinetic model combined with reverse dose method to study the nephrotoxic tolerance dose of tacrolimus

Physiologically based pharmacokinetic model combined with reverse dose method to study the nephrotoxic tolerance dose of tacrolimus

Authors: Cai L, Ke M, Wang H, Wu W, Lin R, Huang P, Lin C
Publication: Arch Toxicol
Keywords: chemical safety, gastroplus, ngra, PBPK modeling, physiologically based pharmacokinetics, reverse dosimetry, risk assessment, toxicokinetics, toxicology
Software: GastroPlus®

Nephrotoxicity is the most common side effect that severely limits the clinical application of tacrolimus (TAC), an immunosuppressive agent used in kidney transplant patients.

The In Vitro, In Vivo, and PBPK Evaluation of a Novel Lung-Targeted Cardiac-Safe Hydroxychloroquine Inhalation Aerogel

The In Vitro, In Vivo, and PBPK Evaluation of a Novel Lung-Targeted Cardiac-Safe Hydroxychloroquine Inhalation Aerogel

Authors: Alsmadi MM, Jaradat N, Obaidat RM, Alnaief M, Tayyem R, Idkaidek N
Publication: AAPS PharmSciTech
Keywords: biopharmaceutics, gastroplus, lung elf, pbbm, PBPK modeling, pcat, physiologically based pharmacokinetics, pulmonary delivery
Software: GastroPlus®

Hydroxychloroquine (HCQ) was repurposed for COVID-19 treatment. Subtherapeutic HCQ lung levels and cardiac toxicity of oral HCQ were overcome...

PB2205: A Mechanistic Absorption and Pharmacokinetic Model of Covalent BTK Inhibitor TL-895: Influence of Food and Acid Reducing Agents

PB2205: A Mechanistic Absorption and Pharmacokinetic Model of Covalent BTK Inhibitor TL-895: Influence of Food and Acid Reducing Agents

Authors: Macwan J, Fraczkiewicz G, Podoll T, Allard M, Krejsa C, Slattter G
Publication: Hemasphere
Keywords: drug pharmacokinetics, drug-drug interactions (DDIs), tyrosine kinase inhibitor
Software: ADMET Predictor®

L-895 is a highly potent, orally available, selective, covalent inhibitor of Bruton tyrosine kinase (BTK) and bone marrow tyrosine kinase X-linked (BMX)...

Quantitative Systems Toxicology identifies independent mechanisms for hepatotoxicity and bilirubin elevations due to AKR1C3 Inhibitor BAY1128688

Quantitative Systems Toxicology identifies independent mechanisms for hepatotoxicity and bilirubin elevations due to AKR1C3 Inhibitor BAY1128688

Authors: Battista C, Shoda LKM, Watkins PB, Groettrup-Wolfers E, Rottmann A, Raschke M, Generaux GT
Publication: Clinical Pharmacology & Therapeutics
Keywords: bile acids, bile salt excretory pump (BSEP), bilirubin, DILIsym, drug-induced liver injury, hepatoxicity, liver toxicity, QST, Quantitative Systems Toxicology (QST), serum alanine aminotransferase (ALT)
Software: DILIsym®
Division: Quantitative Systems Pharmacology (QSP)

BAY1128688 is a selective inhibitor of AKR1C3, investigated recently in a trial that was prematurely terminated due to drug-induced liver injury. These...

Assessing Liver Effects of Cannabidiol and Valproate Alone and in Combination Using Quantitative Systems Toxicology

Assessing Liver Effects of Cannabidiol and Valproate Alone and in Combination Using Quantitative Systems Toxicology

Authors: Lakhani VV, Generaux GT, Howell BA, Longo DM, Watkins PB
Publication: Clin Pharmacol Ther
Keywords: cannabidiol (CBD), CBD, DILIsym, Dravet syndrome, Lennox-Gastaut syndrome, QST, Quantitative Systems Toxicology (QST), seizures, serum alanine aminotransferase (ALT), tuberous sclerosis complex, valproate (VPA)
Software: DILIsym®
Division: Quantitative Systems Pharmacology (QSP)

In clinical trials of cannabidiol (CBD) for the treatment of seizures in patients with Dravet syndrome, Lennox-Gastaut syndrome, and tuberous sclerosis complex, elevations in serum alanine...

Discovering Negative Allosteric Modulators of Frizzled 4 Receptor Using the NPASS Database

Discovering Negative Allosteric Modulators of Frizzled 4 Receptor Using the NPASS Database

Authors: Ni L
Publication: Saint Joseph’s University ProQuest Dissertations Publishing
Keywords: absorption distribution metabolism and excretion (ADME), admet predictor, cancer treatment, tumorigenesis
Software: ADMET Predictor®

The class F G protein-coupled receptors (GPCRs) consists of the Smoothened receptor (SMO) and 10 Frizzled receptors (FZDs).

The Organophosphate Esters Used as Flame Retardants and Plasticizers Affect H295R Adrenal Cell Phenotypes and Functions

The Organophosphate Esters Used as Flame Retardants and Plasticizers Affect H295R Adrenal Cell Phenotypes and Functions

Authors: Li Z, Robaire B, Hales BF
Publication: Endocrinology
Keywords: endocrine disrupting chemicals, H295R human adrenal cells, Organophosphate esters, steroidogenesis
Software: ADMET Predictor®

Adverse effects associated with exposure to brominated flame retardants have led to regulations for their use and their replacement with organophosphate esters (OPEs).

In Silico Modeling Approaches Coupled with In Vitro Characterization in Predicting In Vivo Performance of Drug Delivery System Formulations

In Silico Modeling Approaches Coupled with In Vitro Characterization in Predicting In Vivo Performance of Drug Delivery System Formulations

Authors: Kambayashi A
Publication: Molecular Pharmaceutics
Keywords: biopharmaceutics, biopredictive, gastroplus, in vitro dissolution, IVIVC, pbbm, PBPK modeling, physiologically based pharmacokinetics, z-factor
Software: GastroPlus®

Optimization of the in vivo performance of dosage forms in humans is essential in developing not only conventional formulations but also drug delivery system (DDS) formulations.

Physiologically based pharmacokinetic modeling to assess the drug-drug interactions of anaprazole with clarithromycin and amoxicillin in patients undergoing eradication therapy of H. pylori infection

Physiologically based pharmacokinetic modeling to assess the drug-drug interactions of anaprazole with clarithromycin and amoxicillin in patients undergoing eradication therapy of H. pylori infection

Authors: Liang N, Zhou S, Tongtong Li, Zhang Z, Zhao T, Li R, Li M, Shao F, Wang G, Sun J
Publication: Eur J Pharm Sci
Keywords: Amoxicillin, Anaprazole, clarithromycin, drug-drug interactions (DDIs), physiologically based pharmacokinetics, proton pump inhibitor
Software: GastroPlus®

This study aimed to assess the pharmacokinetic (PK) interactions of anaprazole, clarithromycin, and amoxicillin using physiologically based pharmacokinetic (PBPK) models.