This study evaluated if the intrinsic surface properties of compounds are related to the solubility enhancement (SE) typically observed in biorelevant media like fasted state simulated intestinal fluids (FaSSIF).
In silico optimization of pharmacokinetic properties and receptor binding affinity simultaneously: a ‘parallel progression approach to drug design’ applied to ß-blockers
The present work exploits the potential of in silico approaches for minimizing attrition of leads in the later stages of drug development.
Phenotypic and molecular characterization of circulating tumor cells (CTCs) in patients with castration resistant prostate cancer (CRPC) undergoing treatment with abiraterone acetate or enzalutamide
Despite the introduction of a number of new treatment options (such as abiraterone acetate and enzalutamide) for castration resistant prostate cancer (CRPC), patients with...
Warfarin-dependent gamma-carboxylation regulates androgen receptor activity
The anti-coagulant warfarin prevents the gamma-carboxylation (gla) of target proteins by interfering with the vitamin K cycle through its inhibition of the vitamin K...
Understanding Disease-Drug Interactions in Cancer Patients: Implications for Dosing Within the Therapeutic Window
The human inflammatory response can result in the alteration of drug clearance through effects on metabolizing enzymes or transporters.
In Silico Modeling Can Predict the Unforeseen Renal Failure Caused by SGX523, a c-MET Kinase Inhibitor
SGX523 is a quinoline containing,c-MET kinase inhibitor with an IC50 of 4nM (BuchananSGetal.,2009): Inhibited thegrowth of human glioblastoma lung and gastric cancer xenografts in mice, in a Phase 1 clinical...
Predicting Five Rat Acute Toxicity Endpoints with ANNE Models using ADMET Predictor™
Alternative methods are being explored to predict the toxicity of chemicals to reduce use of animals. Laboratory/Animal tests are costly in time and money, Cheminformatics (QSTR) presents a good alternative to…
The influence of salt chaotropicity, column hydrophobicity and analytes’ molecular properties on the retention of pramipexole and its impurities
The aim of this study was to examine the interaction of the chaotropic salts of different position in Hofmeister series (CF3COONa, NaClO4, NaPF6) added to the mobile phase with the stationary phases of...
Human Exposure Predictions and Food Effect Risk Identification
This GastroPlus™ User Group webinar explores human exposure predictions and food effect risk identification using preclinical data and PBPK models.
Fluorometholone Ocular Suspension PBPK Simulations Using the OCAT™ Model in GastroPlus™
Development of generic formulations of ophthalmic corticosteroids and regulatory acceptance of bioequivalence can be facilitated by analysis of the mechanisms of ocular dissolution, absorption...
Prediction of Pharmacokinetics and Penetration of Moxifloxacin in Human with Intra-Abdominal Infection Based on Extrapolated PBPK Model
The aim of this study is to develop a physiologically based pharmacokinetic (PBPK) model in intra-abdominal infected rats, and extrapolate it to human to predict moxifloxacin pharmacokinetics profiles in...
Design, Synthesis and Pharmacological evaluation of N-[4-(4-(alkyl/aryl/heteroaryl) -piperazin-1-yl) -phenyl] -carbamic acid ethyl ester derivatives as novel anticonvulsant agents
A series of alkyl/aryl/heteroaryl piperazine derivatives (37–54) were designed and synthesized as potential anticonvulsant agents. The target compounds are endowed with satisfactory physicochemical as well as pharmacokinetic properties.
Estimation of the chemical-induced eye injury using a weight-of-evidence (WoE) battery of 21 artificial neural network (ANN) c-QSAR models (QSAR-21): Part I: Irritation potential
Evaluation of potential chemical-induced eye injury through irritation and corrosion is required to ensure occupational and consumer safety for industrial, household and cosmetic ingredient chemicals.
Application of Absorption Modeling to Predict Bioequivalence Outcome of Two Batches of Etoricoxib Tablets
As part of the overall product development and manufacturing strategy, pharmaceutical companies routinely change formulation and manufacturing site.
Prediction of blood-brain barrier permeation of a-adrenergic and imidazoline receptor ligands using PAMPA technique and quantitative-structure permeability relationship analysis
Imidazoline receptor ligands are a numerous family of biologically active compounds known to produce central hypotensive effect by interaction with both α2-adrenoreceptors (α2-AR) and imidazoline receptors (IRs).
Interspecies prediction of oral pharmacokinetics of different formulations from dogs to human: physiologically based pharmacokinetic modelling combined with biorelevant dissolution
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)...
A Population-Based PK/PD Analysis Of Dasotraline Efficacy In The Treatment Of ADHD In Adults
Dasotraline (SEP-225289) is a new chemical entity with a slow elimination half-life demonstrating dopamine (DAT) and norepinephrine (NET) transporter inhibition in clinical studies. Here we hypothesized…
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...