Pre-clinical pharmacokinetics of UK-453,061, a novel non-nucleoside reverse transcriptase inhibitor (NNRTI), and use of in silico physiologically based prediction tools to predict the oral pharmacokinetics of UK-453,061 in man

Pre-clinical pharmacokinetics of UK-453,061, a novel non-nucleoside reverse transcriptase inhibitor (NNRTI), and use of in silico physiologically based prediction tools to predict the oral pharmacokinetics of UK-453,061 in man

Authors: Allan G, Dickins M, Gardner IB, Davis J, Jenkins T, Jones HM, Webster R, Westgate H
Publication: Xenobiotica
Keywords: dog studies, dosage, human clearance, humans, in silico, in vitro, pharmacokinetics, Physiologically based pharmacokinetic (PBPK) modeling, rats
Software: GastroPlus®

UK-453,061 is a novel second-generation non-nucleoside reverse transcriptase inhibitor (NNRTI). Following intravenous bolus administration of UK-453,061 in male rat and infusion administration in dog...

Semimechanistic pharmacokinetic/pharmacodynamic model for hepatoprotective effect of dexamethasone on transient transaminitis after trabectedin (ET-743) treatment

Semimechanistic pharmacokinetic/pharmacodynamic model for hepatoprotective effect of dexamethasone on transient transaminitis after trabectedin (ET-743) treatment

Authors: Fetterly GJ, Owen JS, Stuyckens K, Passarell JA, Zannikos P, Soto-Matos A, Izquierdo MA, Perez Ruixo JJ
Publication: Cancer Chemother Pharmacol
Keywords: body weight, Dexamethasone, hepatocytes, incidence, liver, methods, plasma, population, therapy, Toxicity, Transaminases
Division: Clinical Pharmacology and Pharmacometrics (CPP)
Simulation of Gabapentin Absorption and Bioavailability in Pediatric Patients

Simulation of Gabapentin Absorption and Bioavailability in Pediatric Patients

Authors: Lukacova V, Bolger MB, Woltosz WS
Conference: ISSX
Keywords: absorption, Gabapentin, pediatrics, pharmacokinetics, PK
Software: ADMET Predictor®, GastroPlus®
Division: PBPK

To fit an absorption-pharmacokinetic model for simulation of Gabapentin in adult and pediatric populations. The model will be able to describe the nonlinear dose dependence of absorption mediated by an amino…

Population Pharmacokinetics of Bendamustine and Metabolites in Patients With Indolent Non-Hodgkin Lymphoma

Population Pharmacokinetics of Bendamustine and Metabolites in Patients With Indolent Non-Hodgkin Lymphoma

Authors: Owen JS, Melhem M, D’Andrea D, Darwish M
Conference: ASCPT
Keywords: alkylating agent, antineoplastics, body surface area, BSA, cancer, dose proportionality, intravenous, IV, metabolites, NONMEM, Oncology, PK
Division: Clinical Pharmacology and Pharmacometrics (CPP)

Bendamustine is a bifunctional alkylating agent in development as monotherapy and in combination with other agents in the treatment of indolent non-Hodgkin lymphoma (NHL).

Model Feasibility Assessment as a Driver for Model-Based Drug Development

Model Feasibility Assessment as a Driver for Model-Based Drug Development

Authors: Cirincione B, Blase E, Cummings M, Fineman MS, Grasela TH
Conference: ASCPT
Keywords: antidiabetic agents, database, diabetes, drug development process, efficiency, Endocrinology, exenatide, exendin, forensic pharmacometrics, gap analysis, informatics, PKPD methodology
Division: Clinical Pharmacology and Pharmacometrics (CPP)

Complex pharmacometric analyses raise concerns about cost, time, and reliability of the modelbuilding process (MBP). The goal was to use a model feasibility assessment (MFA) process to improve the performance…

Application of Gastrointestinal Simulation for Extensions for Biowaivers of Highly Permeable Compounds

Application of Gastrointestinal Simulation for Extensions for Biowaivers of Highly Permeable Compounds

Authors: Tubic-Grozdanis M, Bolger MB, Langguth P
Publication: AAPS J
Keywords: absorption, bioavailability, bioequivalence, biowaiver, permeability, solubility
Software: GastroPlus®
Division: PBPK

The goal of this study was to apply gastrointestinal simulation technology and integration of physiological parameters to predict biopharmaceutical drug classification.

The effect of age, gender, and body mass index on the pharmacokinetics and pharmacodynamics of vildagliptin in healthy volunteers

The effect of age, gender, and body mass index on the pharmacokinetics and pharmacodynamics of vildagliptin in healthy volunteers

Authors: He Y, Sabo R, Campestrini J, Wang Y, Riviere GJ, Nielsen JC, Rosenberg M, Ligueros-Saylan M, Howard D, Dole WP
Publication: Br J Clin Pharmacol
Keywords: 80 and over, Adamantane, administration, administration & dosage, adult, aged, aging, analogs & derivatives, BMI, body mass index, comparative study, drug effects, female, humans, male, metabolism, methods, Nitriles, oral, pharmacokinetics, pharmacology, vildagliptin
Division: Clinical Pharmacology and Pharmacometrics (CPP)

What is already known about this subject. Vildagliptin is a new, potent, and selective inhibitor of DPP-4. The efficacy and safety of vildagliptin in type 2 diabetes has been...

Drug Lipophilicity and Microsomal Protein Concentration as Determinants in the Prediction of the Fraction Unbound in Microsomal Incubations

Drug Lipophilicity and Microsomal Protein Concentration as Determinants in the Prediction of the Fraction Unbound in Microsomal Incubations

Authors: Gertz M, Kilford P, Houston JB, Galetin A
Publication: Drug Metab Dispos
Keywords: drug metabolism, lipophilicity, microsomal binding
Division: PBPK

The current study was undertaken to elucidate the relative utility of these prediction tools over a range of drug lipophilicity and microsomal protein concentration.

Novel Hierarchical Classification and Visualization Method for Multiobjective Optimization of Drug Properties: Application to Structure-Activity Relationship Analysis of Cytochrome P450 Metabolism

Novel Hierarchical Classification and Visualization Method for Multiobjective Optimization of Drug Properties: Application to Structure-Activity Relationship Analysis of Cytochrome P450 Metabolism

Authors: Yamashita F, Hara H, Ito T, Hashida M
Publication: J Chem Inf Model
Keywords: ADME/Tox properties, cytochrome P450 (CYP), structure−activity relationships (SAR)
Software: ADMET Predictor®

In the lead optimization process, medicinal chemists must consider various chemical properties of active compounds, including ADME/Tox properties, and find the best compromise among these.