Modeling and simulation to support apixaban dose recommendation for thromboembolism prevention in pediatric subjects with congenital or acquired heart disease requiring anticoagulation–saxophone study

Modeling and simulation to support apixaban dose recommendation for thromboembolism prevention in pediatric subjects with congenital or acquired heart disease requiring anticoagulation–saxophone study

Authors: Ajavon-Hartmann T, Jarugula P, Back H, Obianom O, Ludwig EA, Crevar C, Marchisin D, Wang Z, Chen W, He B, Perera V, Murthy B, Merali S
Conference: ASCPT
Keywords: Apixaban, congenital or acquired heart disease, SAXOPHONE Study
Division: Clinical Pharmacology and Pharmacometrics (CPP)

Apixaban is an oral, direct, selective factor Xa (FXa) inhibitor1 and may be a treatment option for venous thromboembolism prevention in...

Discovery of Clinical Candidate ACT-777991, a Potent CXCR3 Antagonist for Antigen-Driven and Inflammatory Pathologies

Discovery of Clinical Candidate ACT-777991, a Potent CXCR3 Antagonist for Antigen-Driven and Inflammatory Pathologies

Authors: Meyer EA, Äänismaa P, Ertel EA, Hühn E, Strasser DS, Rey M, Murphy MJ, Martinic MM, Pouzol L, Froidevaux S, Keller MP, Caroff E
Publication: J Med Chem
Keywords: admet predictor, discovery pk, FIHSimulator, first-in-human, gastroplus, machine learning, PBPK modeling, physiologically based pharmacokinetics
Software: GastroPlus®

The CXCR3 chemokine receptor is a G protein-coupled receptor mainly expressed on immune cells from the lymphoid lineage, including activated T cells.

A validated PBPK model is used in lieu of clinical studies to assess the risk of CYP3A4-mediated DDIs for an anticancer drug rivoceranib (victim) with weak/moderate CYP3A4 inhibitors (ranitidine/fluconazole), or with a moderate CYP3A4 inducer (efavirenz)

A validated PBPK model is used in lieu of clinical studies to assess the risk of CYP3A4-mediated DDIs for an anticancer drug rivoceranib (victim) with weak/moderate CYP3A4 inhibitors (ranitidine/fluconazole), or with a moderate CYP3A4 inducer (efavirenz)

Authors: Novakovic J, Fraczkiewicz G, Jang SH, Heckman J, Zhou M, Djebli N
Conference: ASCPT

A PBPK model for anticancer drug rivoceranib (RIV), a tyrosine kinase inhibitor (TKI) that selectively targets vascular endothelia growth factor...

CMC development of [14C]-labeled sotorasib for the conduct of microtracer human ADME study

CMC development of [14C]-labeled sotorasib for the conduct of microtracer human ADME study

Authors: Sharma S, Agarwal P, Parsons AT, Huckle JE, Correll TL
Publication: AAPS Open
Keywords: biopharmaceutics, gastroplus, in vitro dissolution, parameter sensitivity analysis, particle size distribution, pbbm, PBPK modeling, physiologically based pharmacokinetics
Software: GastroPlus®

Human absorption, distribution, metabolism, and excretion (hADME) studies of new drugs are required for global regulatory filings.

Liquid Chromatography–Electrospray Ionization Tandem Mass Spectrometry Estimation of Quercetin-Loaded Nanoemulsion in Rabbit Plasma: In Vivo–In Silico Pharmacokinetic Analysis Using GastroPlus

Liquid Chromatography–Electrospray Ionization Tandem Mass Spectrometry Estimation of Quercetin-Loaded Nanoemulsion in Rabbit Plasma: In Vivo–In Silico Pharmacokinetic Analysis Using GastroPlus

Authors: Das SS, Verma PRP, Sekarbabu V, Mohanty S, Pattnaik AK, Ruokolainen J, Kesari KK, Singh SK
Publication: ACS Omega
Keywords: biopharmaceutics, gastroplus, mechanistic ivivc, pbbm, PBPK modeling, physiologically based pharmacokinetics
Software: GastroPlus®

In the present study, we developed and validated a rapid, specific, sensitive, and reproducible liquid chromatography–electrospray ionization tandem mass spectrometry method...

Physiologically Based Pharmacokinetic Modelling to Predict Pharmacokinetics of Enavogliflozin, a Sodium-Dependent Glucose Transporter 2 Inhibitor, in Humans

Physiologically Based Pharmacokinetic Modelling to Predict Pharmacokinetics of Enavogliflozin, a Sodium-Dependent Glucose Transporter 2 Inhibitor, in Humans

Authors: Kim MS, Choi JS, Ji HY, Yang E, Park JS, Kim HS, Kim MJ, Cho IK, Chung SJ, Chae YJ, Lee KR
Publication: Pharmaceutics
Keywords: diabetes mellitus, DWP16001, Enavogliflozin, GCC5694A, in vitro–in vivo extrapolation, mechanistic kidney model, pharmacokinetics, physiologically-based pharmacokinetic modelling, sodium-glucose cotransporter 2 inhibitor
Software: ADMET Predictor®

Enavogliflozin is a sodium-dependent glucose cotransporter 2 (SGLT2) inhibitor approved for clinical use in South Korea.

NAFLDsym v2B Beta Release is Here: Insight into the Next Gen QSP Software Tool in Julia with Blazing Speed and Updated Interfacing

NAFLDsym v2B Beta Release is Here: Insight into the Next Gen QSP Software Tool in Julia with Blazing Speed and Updated Interfacing

Authors: Howell B, Siler SQ, McDaniel MC, Berry C, Huizar F
Keywords: graphical user interface (GUI), modeling and simulation, NAFLDsym v2B Beta, QSP (quantitative systems pharmacology) modeling program, QST modeling, SimPops
Software: NAFLDsym®
Division: Quantitative Systems Pharmacology (QSP)

Join us in this webinar to learn about the technical advances made to the NAFLDsym platform in the latest release: version 2B Beta.

Computational Analysis and Experimental Testing of the Molecular Mode of Action of Gatastatin and Its Derivatives

Computational Analysis and Experimental Testing of the Molecular Mode of Action of Gatastatin and Its Derivatives

Authors: Vottero P, Wang Q, Michalak M, Aminpour M, Tuszynski JA
Publication: Cancer
Keywords: docking, gatastatin, microtubules, molecular dynamics, tubulin
Software: ADMET Predictor®

Given its critical role in cell mitosis, the tubulin chain represents a viable chemotherapeutic target to solve the specificity issues associated with targeting...

Evaluation and prediction of oral drug absorption and bioequivalence with food-druginteraction

Evaluation and prediction of oral drug absorption and bioequivalence with food-druginteraction

Authors: Tsume Y
Publication: Drug Metab Pharmacokinet
Keywords: bioequivalence, biopredictive dissolution method, food effect, gastroplus, pbbm, PBPK modeling, physiologically based biopharmaceutics
Software: GastroPlus®

This article reviews the impacts on the in vivo prediction of oral bioavailability (BA) and bioequivalence (BE) based on Biopharmaceutical classification systems (BCS)...

Predictive Potential of BCS and Pharmacokinetic Parameters on Study Outcome: Analysis of 198 In Vivo Bioequivalence Studies

Predictive Potential of BCS and Pharmacokinetic Parameters on Study Outcome: Analysis of 198 In Vivo Bioequivalence Studies

Authors: Krajcar D, Grabnar I, Jereb R, Legen I, Opara J
Publication: Eur J Drug Metab Pharmacokinet
Keywords: admet predictor, BCS, gastroplus, Peff, permeability
Software: GastroPlus®

Understanding predictive potential of parameters to perform early bioequivalence (BE) risk assessment is crucial for good planning and risk mitigation during product...

A comprehensive regulatory and industry review of modeling and simulation practices in oncology clinical drug development

A comprehensive regulatory and industry review of modeling and simulation practices in oncology clinical drug development

Authors: Ruiz-Garcia A, Baverel P, Dolton MJ, González-García I, Kim J, Robey S, Singh I, Wu SP, Yin D, Zhou D, Zhu H, Bonate P
Publication: J Pharmacokinet Pharmacodyn
Keywords: clinical drug development, drug exposure, exposure-response, Oncology
Division: Clinical Pharmacology and Pharmacometrics (CPP)

Exposure-response (E-R) analyses are an integral component in the development of oncology products.

SeDeM expert system with I-optimal mixture design for oral multiparticulate drug delivery: An encapsulated floating minitablets of loxoprofen Na and its in silico physiologically based pharmacokinetic modeling

SeDeM expert system with I-optimal mixture design for oral multiparticulate drug delivery: An encapsulated floating minitablets of loxoprofen Na and its in silico physiologically based pharmacokinetic modeling

Authors: Rauf-Ur-Rehman, Shoaib MH, Ahmed FR, Yousuf RI, Siddiqui F, Saleem MT, Qazi F, Khan MZ, Irshad A, Bashir L, Naz S, Farooq M, Mahmood ZA
Publication: Front Pharmacol
Keywords: ai, gastro-retentive, gastroplus, pbbm, PBPK modeling, physiologically based biopharmaceutics
Software: GastroPlus®

Introduction: A SeDeM expert tool-driven I-optimal mixture design has been used to develop a directly compressible multiparticulate based extended release minitablets...