The aim of the present study was to use physiologically based pharmacokinetic (PBPK) modelling combined with biorelevant dissolution to quantitatively predict dog oral drug pharmacokinetic (PK)...
Evaluation and comparison of benchmark QSAR models to predict a relevant REACH endpoint: The bioconcentration factor (BCF)
The bioconcentration factor (BCF) is an important bioaccumulation hazard assessment metric in many regulatory contexts. Its assessment is required by the REACH regulation...
Targeting pharmacoresistant epilepsy and epileptogenesis with a dual-purpose antiepileptic drug
In human epilepsy, pharmacoresistance to antiepileptic drug therapy is a major problem affecting a substantial fraction of patients.
Computational Prediction of Drug Solubility in Fasted Simulated and Aspirated Human Intestinal Fluid
To develop predictive models of apparent solubility (Sapp) of lipophilic drugs in fasted state simulated intestinal fluid (FaSSIF) and aspirated human intestinal fluid (HIF).
Simulation of In Vitro Dissolution Behavior Using DDDPlus™
.Dissolution testing is a performance test for many dosage forms including tablets and capsules. The objective of this study was to evaluate if computer simulations can predict the in vitro dissolution of...
Determining Pharmacological Selectivity of the Kappa Opioid Receptor Antagonist LY2456302 Using Pupillometry as a Translational Biomarker in Rat and Human
Selective kappa opioid receptor antagonism is a promising experimental strategy for the treatment of depression.
Concomitant intake of alcohol may increase the absorption of poorly soluble drugs
Ethanol can increase the solubility of poorly soluble and hence present a higher drug concentration in the gastrointestinal tract.
Utilizing Physiologically Based Pharmacokinetic Modeling to Inform Formulation and Clinical Development for a Compound with pH-Dependent Solubility
ARRY-403 is a glucokinase activator developed for the treatment of diabetes. Less than dose-proportional exposure was observed during single ascending dose studies with ARRY-403.
Physiologically based pharmacokinetic modelling in drug discovery and development: A pharmaceutical industry perspective
The application of physiologically based pharmacokinetic (PBPK) modeling has developed rapidly within the pharmaceutical industry and is becoming an integral part of drug discovery and development.
Comparison of in silico tools for evaluating rat oral acute toxicity
Different in silico models have been developed and implemented for the evaluation of mammalian acute toxicity, exploring acute oral toxicity data expressed as median lethal dose (LD(50)).
The potency–insolubility conundrum in pharmaceuticals: Mechanism and solution for hepatitis C protease inhibitors
As compounds are optimized for greater potency during pharmaceutical discovery, their aqueous solubility often decreases, making them less viable as orally-administered drugs.
The potency-insolubility conundrum in pharmaceuticals: Mechanism and solution for hepatitis C protease inhibitors
As compounds are optimized for greater potency during pharmaceutical discovery, their aqueous solubility often decreases, making them less viable as orally-administered drugs.
Relationships between the antidotal efficacy and structure, PK/PD parameters and bio-relevant molecular descriptors of AChE reactivating oximes: inclusion and integration to biopharmaceutical classification systems
The therapeutic outcome of oximes used as reactivators of phosphorylated human acetylcholinesterase (AChE) is influenced, among other factors, by their biological distribution, their in vivo ability...
In vitro-in vivo correlations: general concepts, methodologies and regulatory applications
The major objective of in vitro-in vivo correlations is to be able to use in vitro data to predict in vivo performance serving as a surrogate for an in vivo bioavailability test and to support biowaivers.
Chromatographic lipophilicity as a predictor of antiproliferative activity of 17-picolyl and 17-picolinylidene androstane derivatives toward prostate cancer
Lipophilicity is a molecular parameter widely used in estimation of biological and environmental behavior of many substances (1-3).
Nonclinical and pharmacokinetic assessments to evaluate the potential of tedizolid and linezolid to affect mitochondrial function
Prolonged treatment with the oxazolidinone linezolid is associated with myelosuppression, lactic acidosis, and neuropathies, toxicities likely caused by impairment of mitochondrial protein synthesis (MPS). To evaluate the potential of the novel oxazolidinone tedizolid...
Predicting drug-drug interactions involving multiple mechanisms using physiologically based pharmacokinetic modeling: A case study with ruxolitinib
Physiologically based pharmacokinetic modeling was applied to characterize the potential drug–drug interactions for ruxolitinib.
MITOsym®: A Mechanistic, Mathematical Model of Hepatocellular Respiration and Bioenergetics
MITOsym, a new mathematical model of hepatocellular respiration and bioenergetics, has been developed in partnership with the DILIsym® model with the purpose of translating in vitro compound screening data...
Predicting pharmacokinetics of anti-cancer drug, famitinib in human using physiologically based pharmacokinetic model
This study is to establish physiologically based pharmacokinetic (PBPK) models of famitinib in rat and monkey, and then to predict the pharmacokinetics and tissue distribution of famitinib in human based on the PBPK models.
Computational classification models for predicting the interaction of drugs with P-glycoprotein and breast cancer resistance protein
P-glycoprotein (P-gp/ABCB1) and breast cancer resistance protein (BCRP/ABCG2) are two members of the adenosine triphosphate (ATP) binding cassette (ABC) family of transporters which...