Prediction of Oral Pharmacokinetics of cMet Kinase Inhibitors in Humans: Physiologically Based Pharmacokinetic Model versus Traditional One Compartment Model.

Prediction of Oral Pharmacokinetics of cMet Kinase Inhibitors in Humans: Physiologically Based Pharmacokinetic Model versus Traditional One Compartment Model.

Authors: Yamazaki S, Skaptason J, Romero D, Vekich S, Tan W, Jones HM, Wilner KD, Koudriakova T
Publication: Drug Metab Dispos
Keywords: animals, biological availability, dogs, drug evaluation, heptocyte, humans, metabolic clearance rate, metabolism, oral administration, pharmacokinetics, protein kinase inhibitors, proto-oncogene proteins, pyrazines, pyrazoles, rats
Software: GastroPlus®

The objective of this study was to assess the physiologically based pharmacokinetic (PBPK) model for predicting plasma concentration-time profiles...

Use of structure-activity landscape index curves and curve integrals to evaluate the performance of multiple machine learning prediction models

Use of structure-activity landscape index curves and curve integrals to evaluate the performance of multiple machine learning prediction models

Authors: LeDonne NC Jr, Rissolo K, Bulgarelli J, Tini L
Publication: J Cheminform
Keywords: machine learning method, predictive models, structure-activity landscape index (SALI), structure−activity relationships (SAR)
Software: ADMET Predictor®

Standard approaches to address the performance of predictive models that used common statistical measurements for the entire data set provide an overview of...

Evolving hERG Inhibition Model

Evolving hERG Inhibition Model

Authors: Lee AC, Fraczkiewicz G, Fraczkiewicz R, Clark RD, Woltosz WS
Conference: ACS
Keywords: ADMET, ANNE, artificial neural network ensembles (ANNE), hERG, hERG inhibition, U.S. FDA
Software: ADMET Predictor®
Division: PBPK

Modeling hERG inhibition has significantly gained popularity since 2005, when the FDA recognized the correlation between hERG inhibition and a prolonged QT interval by issuing guidance for the…

Physiologically-Based Pharmacokinetic (PBPK) Model for Prediction of Tobramycin Pulmonary Absorption and Pharmacokinetics in Children

Physiologically-Based Pharmacokinetic (PBPK) Model for Prediction of Tobramycin Pulmonary Absorption and Pharmacokinetics in Children

Authors: Lukacova V, Chaudhuri S, Woltosz WS, Bolger MB
Keywords: absorption, additional dosage routes, ADMET, Cp-Time, PBPK, PEAR, Population Estimates for Age-Related (PEAR™) Physiology™, pulmonary, pulmonary playlist, tissue:plasma, tobramycin
Software: ADMET Predictor®, GastroPlus®
Division: PBPK

To fit an absorption-pharmacokinetic model for simulation of tobramycin in adult and pediatric populations. Tobramycin pulmonary absorption and pharmacokinetics were simulated using GastroPlus™.

Physiologically-based pharmacokinetic {PBPK) models for prediction of time-dependent enzyme inhibition (TDI): effect of diltiazem on midazolam and quinidine

Physiologically-based pharmacokinetic {PBPK) models for prediction of time-dependent enzyme inhibition (TDI): effect of diltiazem on midazolam and quinidine

Authors: Lukacova V, Chung J, Woltosz WS, Bolger MB
Keywords: ACAT model, CYP, diltiazem, midazolam, PBPK model, pharmacokinetic, time-dependent enzyme inhibition (TDI)
Software: GastroPlus®
Division: PBPK

Purpose of the study was to optimize a PBPK model to predict time­dependent and competitive inhibition of CYP 3A4 by diltiazem...

Pharmacokinetics of dietary cancer chemopreventive compound dibenzoylmethane in rats and the impact of nanoemulsion and genetic knockout of Nrf2 on its disposition

Pharmacokinetics of dietary cancer chemopreventive compound dibenzoylmethane in rats and the impact of nanoemulsion and genetic knockout of Nrf2 on its disposition

Authors: Lin W, Hong JL, Shen G, Wu RT, Wang Y, Huang MT, Newmark HL, Huang Q, Khor TO, Heimbach T, Kong AN
Publication: Biopharm Drug Dispos
Keywords: bioavailability, hepatic blood clearance, in vitro-in vivo correlation (IVIVC), intravenous administration, oral administration, pharmacokinetics, rats
Software: GastroPlus®

The pharmacokinetic disposition of a dietary cancer chemopreventive compound dibenzoylmethane (DBM) was studied in male Sprague-Dawley rats after intravenous...

Development of A Mechanistic in vitro – in vivo Correlation for Theophylline

Development of A Mechanistic in vitro – in vivo Correlation for Theophylline

Authors: Chung J, Lukacova V, Bolger MB, Woltosz WS
Conference: AAPS
Keywords: ACAT model, Advanced Compartmental Absorption and Transit (ACAT™) model, In vitro in vivo correlations (IVIVC), intravenous, IVIVC, lung diseases, PBPK, Theophylline
Software: GastroPlus®
Division: PBPK

Theophylline is used to prevent and treat wheezing, shortness of breath, and difficulty breathing caused by asthma, chronic bronchitis, emphesema, and other lung diseases. Immediate release oral…

Application of a Respiratory PBPK Model for Predicting Deposition and Disposition following Inhaled Administration of Morphine

Application of a Respiratory PBPK Model for Predicting Deposition and Disposition following Inhaled Administration of Morphine

Authors: Chaudhuri S, Lukacova V, Woltosz WS
Conference: AAPS
Keywords: ACAT, additional dosage routes, Advanced Compartmental Absorption and Transit (ACAT™) model, inhaled, PBPK, pulmonary
Software: GastroPlus®
Division: PBPK

Demonstrate the pulmonary component of the GastroPlus™ Additional Dosage Routes Module™ (ADRM) simulation to develop a pharmacokinetic (PK) and pharmacodynamic (PD) model for inhaled…

Mechanistic PBPK Simulation in Place of In Vivo Drug-Drug Interaction (DDI) Studies for Compliance with Regulatory Requirements of EMA and FDA

Mechanistic PBPK Simulation in Place of In Vivo Drug-Drug Interaction (DDI) Studies for Compliance with Regulatory Requirements of EMA and FDA

Authors: Bolger MB, Woltosz WS, Lukacova V, Chung J, Zhou H, Fraczkiewicz G, Lavé T, Parrott N
Conference: AAPS
Keywords: DDIs, drug-drug interactions (DDIs), European Medicines Agency (EMA), PBPK, PBPK modeling, U.S. FDA
Software: GastroPlus®
Division: PBPK

To highlight the application and validation of PBPK DDI simulation results obtained using GastroPlus™ in compliance with newly proposed European Medicines Agency (EMA) and US FDA guidelines for the…

Bendamustine pharmacokinetic profile and exposure-response relationships in patients with indolent non-Hodgkin’s lymphoma

Bendamustine pharmacokinetic profile and exposure-response relationships in patients with indolent non-Hodgkin’s lymphoma

Authors: Owen JS, Melhem M, Passarell JA, D’Andrea D, Darwish M, Kahl B
Publication: Cancer Chemother Pharmacol
Keywords: alkylating agent, body surface area, BSA, cancer, dose proportionality, drug-resistant cancer, intravenous, IV, metabolites, NONMEM, PK
Division: Clinical Pharmacology and Pharmacometrics (CPP)

The pharmacokinetic profiles of bendamustine and active metabolites were defined in patients with rituximab-refractory, relapsed indolent B-cell non-Hodgkin's lymphoma, and supported understanding of exposure-response relationships for efficacy and safety.