Targeting Plague Virulence Factors: A Combined Machine Learning Method and Multiple Conformational Virtual Screening for the Discovery of Yersinia Protein Kinase A Inhibitors

Targeting Plague Virulence Factors: A Combined Machine Learning Method and Multiple Conformational Virtual Screening for the Discovery of Yersinia Protein Kinase A Inhibitors

Authors: Hu X, Prehna G, Stebbins CE
Publication: J Med Chem
Keywords: anti-plague drugs, high-throughput docking, machine learning method, Yersinia protein kinase A (YpkA)
Software: ADMET Predictor®

Yersinia spp. is currently an antibiotic resistance concern and a re-emerging disease.

Pharmacometrics and the transition to model-based development

Pharmacometrics and the transition to model-based development

Keywords: analysis, animals, clinical, computer simulation, data_assembly_and_programming, Drug Approval, drug design, Drug Information Services, humans, methods, models, New York, pharmacology, statistics & numerical data, Theoretical
Division: Clinical Pharmacology and Pharmacometrics (CPP)

As the transition to model-based drug development continues, pharmacometric analysis will have an increasingly important role across the entire life cycle of drug discovery...

Effect of Formulation on Adinazolam Pharmacokinetics and Pharmacodynamics

Effect of Formulation on Adinazolam Pharmacokinetics and Pharmacodynamics

Authors: Lukacova V, Fraczkiewicz G, Prabhakaran A, Bolger MB, Woltosz WS
Conference: CRS
Keywords: Adinazolam, controlled release, dissolution testing, oral, oral dose, PD, pharmacodynamics (PD), pharmacokinetics (PK), PK
Software: DDDPlus™, GastroPlus®
Division: PBPK

Adinazolam has been reported to have anxiolytic and antidepressant properties [1]. Numerous pharmacokinetic (PK) and pharmacodynamic (PD) studies of immediate release as well as sustained release…

Designing In Vitro Dissolution Tests to Better Mimic In Vivo Release

Designing In Vitro Dissolution Tests to Better Mimic In Vivo Release

Authors: Woltosz WS, Lukacova V, Prabhakaran A, DiBella J, Bolger MB
Conference: CRS
Keywords: absorption, controlled release, Cp-Time, dissolution, dissolution testing, metabolism, USP
Software: DDDPlus™, GastroPlus®
Division: PBPK

In vitro dissolution tests were traditionally designed for quality control. USP methods commonly used to evaluate the release rate of new controlled release dosage forms are often based on such experiments.

Pharmacokinetics and pharmacodynamics of vildagliptin in patients with type 2 diabetes mellitus

Pharmacokinetics and pharmacodynamics of vildagliptin in patients with type 2 diabetes mellitus

Authors: He YL, Serra D, Wang Y, Campestrini J, Riviere GJ, Deacon CF, Holst JJ, Schwartz S, Nielsen JC, Ligueros-Saylan M
Publication: Clin Pharmacokinet
Keywords: Adamantane, administration, administration & dosage, adult, adverse effects, aged, analogs & derivatives, area under curve, blood, Blood Glucose, chemically induced, cross-over studies, diabetes mellitus, Dose-Response Relationship, Doubl, drug, oral, type 2
Division: Clinical Pharmacology and Pharmacometrics (CPP)

Vildagliptin is a dipeptidyl peptidase IV (DPP-4) inhibitor currently under development for the treatment of type 2 diabetes mellitus.

The Application of Systematic Analysis for Identifying and Addressing the Needs of the Pharmacometric Process

The Application of Systematic Analysis for Identifying and Addressing the Needs of the Pharmacometric Process

Authors: Grasela TH
Conference: PAGE
Keywords: communications, data assembly, dataset creation, dataset requirements, enterprise engineering, forensic pharmacometrics, gap analysis, informatics, PKPD methodology, process, team
Division: Clinical Pharmacology and Pharmacometrics (CPP)

The current implementation of a pharmacometric process has, in most cases, grown from the ad hoc application of modeling and simulation activities to the drug-development process. This ad hoc…

Mechanism-Based Pharmacokinetic / Pharmacodynamic Model for Hepatoprotective Effect of Dexamethasone on Transient Transaminitis After Trabectedin (ET-743, Yondelis®) Treatment

Mechanism-Based Pharmacokinetic / Pharmacodynamic Model for Hepatoprotective Effect of Dexamethasone on Transient Transaminitis After Trabectedin (ET-743, Yondelis®) Treatment

Authors: Fetterly GJ, Owen JS, Stuyckens K, Passarell JA, Zannikos P, Soto-Matos A, Izquierdo MA, Perez Ruixo JJ
Conference: ASCO
Keywords: ALT, antineoplastics, cancer, dose reduction, heptocyte, indirect response model, intravenous, IV, liver, mixture model, Oncology, PK/PD, precursor-dependent model, safety, simulation, time course
Division: Clinical Pharmacology and Pharmacometrics (CPP)

Reversible transient elevations in transaminases have been observed after trabectedin (T) administration, despite no alteration in plasma PK. A PKPD model was developed to evaluate the time course of ALT elevation…

Population pharmacokinetics of tigecycline in healthy volunteers

Population pharmacokinetics of tigecycline in healthy volunteers

Authors: Van Wart S, Cirincione BB, Ludwig EA, Meagher AK, Korth-Bradley JM, Owen JS
Publication: J Clin Pharmacol
Keywords: adolescent, adult, aged, analogs & derivatives, anti-bacterial agents, area under curve, biological, blood, clinical trials, drug administration schedule, female, humans, male, middle-aged, Minocycline, models, multicenter studies, Phase I as Topic
Division: Clinical Pharmacology and Pharmacometrics (CPP)

Tigecycline, a novel glycylcycline, possesses broad-spectrum antimicrobial activity. A structural population pharmacokinetic model for tigecycline...

The Prediction of Drug Metabolism, Tissue Distribution, and Bioavailability of 50 Structurally Diverse Compounds in Rat Using Mechanism-Based Absorption, Distribution, and Metabolism Prediction Tools

The Prediction of Drug Metabolism, Tissue Distribution, and Bioavailability of 50 Structurally Diverse Compounds in Rat Using Mechanism-Based Absorption, Distribution, and Metabolism Prediction Tools

Authors: De Buck SS, Sinha VK, Fenu LA, Gilissen RA, Mackie CE, Nijsen MJ
Publication: Drug Metab Dispos
Keywords: bioavailability, hepatic blood clearance, oral bioavailability, pharmacokinetics, physiologically based prediction, rat
Software: ADMET Predictor®, GastroPlus®

The aim of this study was to assess a physiologically based modeling approach for predicting drug metabolism, tissue distribution, and bioavailability in rat for a structurally diverse set of...