Predicting the pharmacokinetics and pharmacodynamics of antisense oligonucleotides: an overview of various approaches and opportunities for PBPK/PD modelling

Predicting the pharmacokinetics and pharmacodynamics of antisense oligonucleotides: an overview of various approaches and opportunities for PBPK/PD modelling

Authors: Gao X, Diep JK, Norris DA, Yu RZ, Geary RS
Publication: Expert Opin Drug Metab Toxicol
Keywords: dose selection, gastroplus, PBPK modeling, pbpk/pd, pharmacodynamics, physiologically based pharmacokinetics, PK/PD, tissue concentrations
Software: GastroPlus®

Advances in research and development (R&D) have enabled many approvals of antisense oligonucleotides (ASOs). Its administration expanded from systemic to local for treating various diseases, where predicting target tissue exposures and pharmacokinetics (PK) and pharmacodynamics (PD) in human can be critical.

Physiologically Based Pharmacokinetic modelling of drugs in pregnancy: A mini-review on availability and limitations

Physiologically Based Pharmacokinetic modelling of drugs in pregnancy: A mini-review on availability and limitations

Authors: Berezowska M, Sharma P, Pilla Reddy V, Coppola P
Publication: Fundam Clin Pharmacol
Keywords: fetus, gastroplus, neonates, PBPK modeling, physiologically based pharmacokinetics, pregnant women, special populations
Software: GastroPlus®

Physiologically based pharmacokinetic (PBPK) modelling in pregnancy is a relatively new approach that is increasingly being used to assess drug systemic exposure in pregnant women to potentially inform dosing adjustments.

ILDSYM®, A Quantitative Systems Pharmacology (QSP) Platform, Successfully Simulates Efficacy of Key Treatments for Systemic Sclerosis-Interstitial Lung Disease

ILDSYM®, A Quantitative Systems Pharmacology (QSP) Platform, Successfully Simulates Efficacy of Key Treatments for Systemic Sclerosis-Interstitial Lung Disease

Authors: Kenz Z, Yang K, Battista C, Shoda LKM, Siler SQ
Conference: ACoP
Keywords: ACoP2023, ILDsym, interstitial lung disease (ILD), lung diseases, nintedanib, quantitative systems pharmacology (QSP), systemic sclerosis, Systemic Sclerosis-Interstitial Lung Disease (SSc-ILD), Tocilizumab
Software: ILDsym™
Division: Quantitative Systems Pharmacology (QSP)

Systemic sclerosis (SSc) is a rare connective tissue and autoimmune disease associated with inflammation of the skin and internal organs. Interstitial lung disease (ILD), a frequent complication of SSc with highly variable course, is associated with increased morbidity and mortality risk¹. Two FDA-approved treatments, anti-inflammatory tocilizumab (TCZ) and anti-fibrotic nintedanib (NIN)...

Accelerating a QSP Model of Nonalcoholic Steatohepatitis (NASH) Using the Julia Language

Accelerating a QSP Model of Nonalcoholic Steatohepatitis (NASH) Using the Julia Language

Authors: McDaniel MC, Generaux GT, Huizar F, Berry C, Siler SQ
Conference: ACoP
Keywords: ACoP2023, Julia, Matlab, NAFLD, NAFLDsym, NASH, quantitative systems pharmacology (QSP)
Software: NAFLDsym®
Division: Quantitative Systems Pharmacology (QSP)

NAFLDsym® is a quantitative systems pharmacology (QSP) platform that simulates progression and treatment of nonalcoholic fatty liver...

Contribution of the Dynamic Intestinal Absorption Model (Diamod) to the Development of a Patient-Centric Drug Formulation

Contribution of the Dynamic Intestinal Absorption Model (Diamod) to the Development of a Patient-Centric Drug Formulation

Authors: Moens F, Larsson A, De Blaiser A, Vandevijver G, Spreafico F, Nicolas JM, Lacombe L, Segregur D, Flanagan T, Berben P
Publication: Mol Pharm
Keywords: biopharmaceutics, formulation assessment, gastroplus, in vitro dissolution, mechanistic absorption, pbbm, PBPK modeling, physiologically based biopharmaceutics
Software: GastroPlus®

Compound X is a weak basic drug targeting the early stages of Parkinson’s disease, for which a theoretical risk assessment has indicated that elevated gastric pH conditions could potentially result in reduced plasma concentrations.

Mechanistic Representation of NAG Release in Relation to Renal Proximal Tubular Cellular Injury

Mechanistic Representation of NAG Release in Relation to Renal Proximal Tubular Cellular Injury

Authors: Hamzavi N, Bhargava P, Stahl SH, Howell BA, Woodhead JL
Conference: American Society of Nephrology (ASN) Kidney Week
Keywords: Acute kidney injury (AKI), cisplatin, CsA, Kidney Week, N-acetyl-beta-D-glucosaminidase, NAG, Quantitative Systems Toxicology (QST), renal injury, RENAsym
Software: RENAsym®
Division: Quantitative Systems Pharmacology (QSP)

Novel Acute kidney injury (AKI) biomarkers enhance disease understanding and aid...

Comparison of monoclonal antibody disposition predictions using different physiologically based pharmacokinetic modelling platforms

Comparison of monoclonal antibody disposition predictions using different physiologically based pharmacokinetic modelling platforms

Authors: De Sutter PJ, Gasthuys E, Vermeulen A
Publication: J Pharmacokinet Pharmacodyn
Keywords: biologics, gastroplus, Injectables, injections, large molecules, PBPK modeling, physiologically based pharmacokinetics, tissue concentrations, translational pk
Software: GastroPlus®

Physiologically based pharmacokinetic (PBPK) models can be used to leverage physiological and in vitro data to predict monoclonal antibody (mAb) concentrations in serum and tissues.

Comparison of monoclonal antibody disposition predictions using different physiologically based pharmacokinetic modelling platforms

Comparison of monoclonal antibody disposition predictions using different physiologically based pharmacokinetic modelling platforms

Authors: De Sutter PJ, Gasthuys E, Vermeulen A
Publication: J Pharmacokinet Pharmacodyn
Keywords: antibodies, biologics, gastroplus, mab, PBPK modeling, physiologically based pharmacokinetics, tissue concentrations
Software: GastroPlus®

Physiologically based pharmacokinetic (PBPK) models can be used to leverage physiological and in vitro data to predict monoclonal antibody (mAb) concentrations in serum and tissues.

Use of In silico Methodologies to Predict the Bioavailability of Oral Suspensions: A Regulatory Approach

Use of In silico Methodologies to Predict the Bioavailability of Oral Suspensions: A Regulatory Approach

Authors: Honório TDS, Simon A, Machado RMC, Rodrigues CR, do Carmo FA, Cabral LM, de Sousa VP
Publication: Curr Pharm Des
Keywords: ACAT, dissolution specifications, gastroplus, IVIVC, mechanistic absorption, pbbm, PBPK modeling, physiologically based biopharmaceutics
Software: GastroPlus®

Oral suspensions are heterogeneous disperse systems, and the particle size distribution, crystalline form of the dispersed solid, and composition of the formulation can be listed as parameters that control the drug dissolution rate and its bioavailability.

Voices in Molecular Pharmaceutics: Meet Dr. Bart Hens, A Sociable Scientist Focusing on Multidisciplinary Connections to Unravel the Gaps of Oral Drug Behavior in the Human Gastrointestinal Tract

Voices in Molecular Pharmaceutics: Meet Dr. Bart Hens, A Sociable Scientist Focusing on Multidisciplinary Connections to Unravel the Gaps of Oral Drug Behavior in the Human Gastrointestinal Tract

Authors: Hens B
Publication: Mol Pharm
Keywords: biopharmaceutics, gastroplus, pbbm, PBPK modeling, physiologically based pharmacokinetics
Software: GastroPlus®

Bart Hens (Pharm.D., Ph.D.) holds a Ph.D. degree in Pharmaceutical Sciences obtained from KU Leuven (Supervisor: Prof. Dr. Patrick Augustijns - Leuven, Belgium).

Repurposing of Strychnine as the Potential Inhibitors of Aldo–keto Reductase Family 1 Members B1 and B10: Computational Modeling and Pharmacokinetic Analysis

Repurposing of Strychnine as the Potential Inhibitors of Aldo–keto Reductase Family 1 Members B1 and B10: Computational Modeling and Pharmacokinetic Analysis

Authors: Sarfraz M, Aziz M, Afzal S, Channar PA, Alsfouk BA, Kandhro GA, Hassan S, Sultan A, Hamad A, Arafat M, Qaiser MN, Ahmed A, Siddiqui F, Ejaz SA
Publication: Protein J
Keywords: admet predictor, gastroplus, high throughput pharmacokinetics, HTPK, PBPK modeling, physiologically based pharmacokinetics
Software: ADMET Predictor®, GastroPlus®

AKR1B1 and AKR1B10 are important members of aldo–keto reductase family which plays a significant role in cancer progression by modulating cellular metabolism.