The Synthetic Cathinones MDPHP and MDPV: Comparison of the Acute Effects in Mice, in silico ADMET Profiles and Clinical Reports

The Synthetic Cathinones MDPHP and MDPV: Comparison of the Acute Effects in Mice, in silico ADMET Profiles and Clinical Reports

Authors: Bassi M, Bilel S, Tirri M, Corli G, Di Rosa F, Gregori A, Alkilany AM, Rachid O, Roda E, De Luca F, Papa P, Buscaglia E, Zauli G, Locatelli CA, Marti M
Publication: Neurotoxicology
Keywords: 4-methylenedioxy-alpha-pyrrolidinohexanophenone, ADMET prediction, admet predictor, aggressivity, behaviour, cardiovascular effect, human intoxication, Synthetic cathinones
Software: ADMET Predictor®
Division: Cheminformatics

The 3,4-methylenedioxy-alpha-pyrrolidinohexanophenone (MDPHP) is a synthetic cathinone closely related to 3,4-methylenedioxypyrovalerone (MDPV), one of the most common synthetic cathinones present in the "bath salts".

Toward Personalized Salbutamol Therapy: Validating Virtual Patient-Derived Population Pharmacokinetic Model with Real-World Data

Toward Personalized Salbutamol Therapy: Validating Virtual Patient-Derived Population Pharmacokinetic Model with Real-World Data

Authors: Marques L, Vale N
Publication: Pharmaceutics
Keywords: admet predictor, dose selection, gastroplus, mechanistic absorption, PBPK modeling, physiologically based pharmacokinetics, PopPK, population simulations
Software: GastroPlus®
Division: PBPK

Interindividual variability, influenced by patient-specific factors including age, weight, gender, race, and genetics, among others, contributes to variations in therapeutic response.

Parameterization of Physiologically Based Biopharmaceutics Models: Workshop Summary Report

Parameterization of Physiologically Based Biopharmaceutics Models: Workshop Summary Report

Authors: Pepin X, Arora S, Borges L, Cano-Vega M, Carducci T, Chatterjee P, Chen G, Cristofoletti R, Dallmann A, Delvadia P, Dressman J, Fotaki N, Gray E, Heimbach T, Holte O, Kijima S, Kotzagiorgis E, Lennernäs H, Lindahl A, Loebenberg R, Mackie C, Malamatari M, McAllister M, Mitra A, Moody R, Mudie D, Musuamba Tshinanu F, Polli JE, Rege B, Ren X, Rullo G, Scherholz ML, Song I, Stillhart C, Suarez-Sharp S, Tannergren C, Tsakalozou E, Veerasingham S, Wagner C
Publication: Mol Pharm
Keywords: bioequivalence, dissolution specifications, gastroplus, mechanistic absorption, pbbm, PBPK modeling, physiologically based biopharmaceutics modeling, regulatory interaction, safe space, vbe
Software: GastroPlus®
Division: PBPK

This Article shares the proceedings from the August 29th, 2023 (day 1) workshop “Physiologically Based Biopharmaceutics Modeling (PBBM) Best Practices for Drug Product Quality: Regulatory and Industry Perspectives”.

Best of both worlds: An expansion of the state of the art pKa model with data from three industrial partners

Best of both worlds: An expansion of the state of the art pKa model with data from three industrial partners

Authors: Fraczkiewicz R, Nguyen HQ, Wu N, Kausch-Busiesc N, Grimbs S, Sommer K, ter Laak A, Gunther J, Wagner B, Reutlinger M
Publication: Mol Inform
Keywords: admet predictor, Bayer CropScience, F. Hoffmann-La Roche, Genentech, In silico pKa prediction, pKa, S+pKa
Software: ADMET Predictor®
Division: Cheminformatics

In a unique collaboration between Simulations Plus and several industrial partners, we were able to develop a new version 11.0 of the previously published in silico pKa model, S+pKa, with considerably improved prediction accuracy

Prediction of Disease Progression and Clinical Response in Systemic Sclerosis: Experience From a Proof-of-Concept Trial

Prediction of Disease Progression and Clinical Response in Systemic Sclerosis: Experience From a Proof-of-Concept Trial

Authors: Neve M, Diderichsen PM, de Vries D, Taneja A
Publication: American College of Rheumatology
Keywords: clinical trial simulation, disease progression, idiopathic pulmonary fibrosis, Proof-of-Concept Trial, systemic sclerosis

Using the modified Rodnan skin score (mRSS) as a surrogate for disease activity, a phase 2a study in patients with systemic sclerosis (SSc) measured efficacy of the autotaxin inhibitor ziritaxestat.

Assessing the Anticholinergic Cognitive Burden Classification of Putative Anticholinergic Drugs Using Drug Properties

Assessing the Anticholinergic Cognitive Burden Classification of Putative Anticholinergic Drugs Using Drug Properties

Authors: Phutietsile GO, Fotaki N, Nishtala PS
Publication: Br J Clin Pharmacol
Keywords: admet predictor, anticholinergic cognitive burden, antimuscarinic, elderly, in silico, machine learning, polypharmacy.
Software: ADMET Predictor®
Division: Cheminformatics

This study evaluated the use of machine learning to leverage drug absorption, distribution, metabolism and excretion (ADME) data together with physicochemical and pharmacological data to develop a novel anticholinergic burden scale and compare its performance to previously published scales.

Application of Mechanistic Pharmacokinetic Model for the Optimization of Metformin Delayed Release Dosage Form for Intestinal Targeting

Application of Mechanistic Pharmacokinetic Model for the Optimization of Metformin Delayed Release Dosage Form for Intestinal Targeting

Authors: Malayandi R, Joseph A, Akbar S, Natesan K, Velayutham R
Publication: Indian J Pharma Education Res
Keywords: biopharmaceutics, extended release, formulation design, gastrointestinal disease, gastroplus, local exposure, pbbm, PBPK modeling, physiologically based pharmacokinetics
Software: GastroPlus®
Division: PBPK

Metformin (MET) is a widely prescribed drug for managing Type 2 Diabetes Mellitus (T2DM). Despite the rich clinical experience and advantages, the clinical utility of MET in renal failure patients is limited because of the treatment-related side effects.

Investigative analysis of blood–brain barrier penetrating potential of electronic nicotine delivery systems (e-cigarettes) chemicals using predictive computational models

Investigative analysis of blood–brain barrier penetrating potential of electronic nicotine delivery systems (e-cigarettes) chemicals using predictive computational models

Authors: Stratford K, Kang JC, Healy SM, Tu Z, Valerio LG Jr
Publication: Expert Opin Drug Metab Toxicol
Keywords: adme prediction, admet predictor, bbb prediction, chemical risk assessment, high throughput pharmacokinetics, HTPK, machine learning, partition coefficients, swiftpk, transporters
Software: ADMET Predictor®
Division: Cheminformatics

Seizures are known potential side effects of nicotine toxicity and have been reported in electronic nicotine delivery systems (ENDS, e-cigarettes) users, with the majority involving youth or young adults.

Physiologically-Based Pharmacokinetic Modelling to Investigate the Effect of CYP3A4/3A5 Maturation on Tacrolimus Pharmacokinetics in Paediatric HSCT Patients

Physiologically-Based Pharmacokinetic Modelling to Investigate the Effect of CYP3A4/3A5 Maturation on Tacrolimus Pharmacokinetics in Paediatric HSCT Patients

Authors: Guan Y, Liu X, Huang K, Wang Y, Qiu K, Wang X, Huang M, Zhou D, Yu X, Zhong G
Publication: Eur J Pharm Sci
Keywords: children, cytochrome P450, dose selection, enzyme ontogeny, gastroplus, PBPK modeling, physiologically based pharmacokinetics, special populations
Software: GastroPlus®
Division: PBPK

Tacrolimus (FK506) is a cornerstone of GVHD-prophylaxis treatment in paediatrics undergoing haematopoietic stem cell transplantation (HSCT).

Prediction of the Liver Safety Profile of a First-in-Class Myeloperoxidase Inhibitor Using Quantitative Systems Toxicology Modeling

Prediction of the Liver Safety Profile of a First-in-Class Myeloperoxidase Inhibitor Using Quantitative Systems Toxicology Modeling

Authors: Woodhead JL, Gebremichael Y, Macwan J, Qureshi IA, Bertz R, Wertz V, Howell BA
Conference: SOT
Keywords: bile acid transporters, DILIsym, liver enzymes, liver safety, liver toxicity, machine learning PBPK QST(P) marriage, mitochondrial function, MITOsym, neurodegenerative disease, neuroinflammatory disease, PBPK, Quantitative Systems Toxicology (QST), SimPops, verdiperstat
Software: DILIsym®, MITOsym®
Division: Quantitative Systems Pharmacology (QSP)

The novel myeloperoxidase inhibitor verdiperstat was developed as a treatment for...

Integrating Human Biomimetic Liver Microphysiology System with Quantitative Systems Toxicology Modeling to Predict DILI

Integrating Human Biomimetic Liver Microphysiology System with Quantitative Systems Toxicology Modeling to Predict DILI

Authors: Yang K
Conference: Discovery Toxicology
Keywords: DILI, DILIsym, human liver microphysiology system, immune checkpoint inhibitors, Quantitative Systems Toxicology (QST), Tocilizumab
Software: DILIsym®
Division: Quantitative Systems Pharmacology (QSP)

Integrating Human Biomimetic Liver Microphysiology System with Quantitative Systems Toxicology Modeling to Predict DILI

Pemvidutide, a glucagon-like peptide 1/glucagon dual receptor agonist, improves metabolic dysfunction-associated steatohepatitis activity and fibrosis in a clinical quantitative systems pharmacology model

Pemvidutide, a glucagon-like peptide 1/glucagon dual receptor agonist, improves metabolic dysfunction-associated steatohepatitis activity and fibrosis in a clinical quantitative systems pharmacology model

Authors: Harrison S, Suschak J, McDaniel MC, Kenz Z, Tomah S, Roberts MS, Siler SQ, Harris MS, Browne S
Conference: EASL Congress
Keywords: fibrosis, MASH, MASLD, NAFLDsym, Pemvidutide, peptide, QSP (quantitative systems pharmacology), QSP (quantitative systems pharmacology) modeling program, steatohepatitis
Software: NAFLDsym®
Division: Quantitative Systems Pharmacology (QSP)

Elevated liver fat content (LFC) is the primary pathophysiologic driver of metabolic dysfunction-associated steatohepatitis (MASH). In prior clinical trials, pemvidutide...