Ammonium, 2,3,3,3-tetrafluoro-2-(heptafluoropropoxy)-propanoate has been developed as a processing aid used in the manufacture of fluoropolymers.
Evaluations of imidazolium ionic liquids as novel skin permeation enhancers for drug transdermal delivery
In this work, imidazolium ionic liquids (imidazolium ILs) were employed as the novel chemical permeation enhancers (CPEs) and their performances and mechanisms of action were deeply investigated.
Some factors that can lead to poor peak shape in hydrophilic interaction chromatography, and possibilities for their remediation
Some factors which present difficulties for obtaining good peak shape in hydrophilic interaction chromatography (HILIC) were studied.
Identification of Novel Potential Inhibitors of Aldose Reductase: A Multistage Computational Filtering Approach
The aldose reductase (AR) is a rate limiting enzyme in the polyol pathway, for the conversion of glucose to sorbitol. The identification of a potent inhibitor is the need of the hour.
A Workflow to Investigate Exposure and Pharmacokinetic Influences on High-Throughput in Vitro Chemical Screening Based on Adverse Outcome Pathways
Adverse outcome pathways (AOPs) link adverse effects in individuals or populations to a molecular initiating event (MIE) that can be quantified using in vitro methods.
Comparison of biorelevant simulated media mimicking the intestinal environment to assess the solubility profiles of poorly soluble drugs
During the discovery stage in lead identification/optimization, compounds are characterized for their solubilities in biorelevant media and these data are often used to model the in vivo behavior of...
Absorption, Metabolism, Excretion, and the Contribution of Intestinal Metabolism to the Oral Disposition of [14C]Cobimetinib, a MEK Inhibitor, in Humans
The pharmacokinetics, metabolism, and excretion of cobimetinib, a MEK inhibitor, were characterized in healthy male subjects (n = 6) following a single 20 mg (200 μCi) oral dose.
Solidified SNEDDS of loratadine: Formulation using hydrophilic and hydrophobic grades of Aerosil®, pharmacokinetic evaluations and in vivo-in silico predictions using GastroPlus
In the present study, hydrophilic and hydrophobic grades of Aerosil® were employed as adsorbents to develop a solid self-nanoemulsifying drug delivery system (S-SNEDDS) of loratadine and were...
A canine biorelevant dissolution method for predicting in vivo performance of orally administered sustained release matrix tablets
Preclinical species are a crucial component of drug development, but critical differences in physiology and anatomy need to be taken into account when attempting to extrapolate to humans or between species.
The potential of immobilized artificial membrane chromatography to predict human oral absorption
The potential of immobilized artificial membrane (IAM) chromatography to estimate human oral absorption (%HOA) was investigated.
Elucidating Differences in the Hepatotoxic Potential of Tolcapone and Entacapone With DILIsym(®), a Mechanistic Model of Drug-Induced Liver Injury.
Tolcapone and entacapone are catechol-O-methyltransferase (COMT) inhibitors developed as adjunct therapies for treating Parkinson's disease.
Biomarker exposure-response relationships as the basis for rational dose selection: Lessons from a simulation exercise using a selective COX-2 inhibitor
An exposure-response model was used to characterize the pharmacokinetic-pharmacodynamic relationship of GW406381, a COX-2 inhibitor, based on data from ex vivo...
Development of a unified dissolution and precipitation model and its use for the prediction of oral drug absorption
Drug absorption is a complex process involving dissolution and precipitation, along with other kinetic processes.
Mitigation of Adverse Clinical Events of a Narrow Target Therapeutic Index Compound through Modified Release Formulation Design: An In Vitro, In Vivo, In Silico, and Clinical Pharmacokinetic Analysis
BMS-914392 is a tricyclic pyranoquinoline BCS class 2 weak base that demonstrates high solubility in low pH environments. Initial clinical studies indicated that rapid release of high dose BMS-914392 led to...
Analysis of Intra- and Intersubject Variability in Oral Drug Absorption in Human Bioequivalence Studies of 113 Generic Products
In this study, the data of 113 human bioequivalence (BE) studies of immediate release (IR) formulations of 74 active pharmaceutical ingredients (APIs) conducted at Sawai Pharmaceutical Co., Ltd., was...
Radiosynthesis and evaluation of N-(3,4-dimethylisoxazol-5-yl)piperazine-4-[4-(4-fluorophenyl)thiazol-2-yl]-1-[11C]carboxamide for in vivo positron emission tomography imaging of fatty acid amide hydrolase in brain
We developed a novel positron emission tomography (PET) radiotracer N-(3,4-dimethylisoxazol-5-yl)piperazine-4-[4-(4-fluorophenyl)thiazol-2-yl]-1-[11C]carboxamide ([11C]DPFC, [11C]1) for in vivo...
Identification of a major radiometabolite of [11C]PBB3
[11C]PBB3 is a clinically used positron emission tomography (PET) probe for in vivo imaging of tau pathology in the brain. Our previous study showed that [11C]PBB3 was rapidly decomposed to...
Effect of SI-591, a new class of cathepsin K inhibitor with peptidomimetic structure, on bone metabolism in vitro and in vivo
SI-591[N-[1-[[[(1S)-3-[[(3S)-hexahydro-2-oxo-1H-azepin-3-yl]amino]-1-(1-methylethyl)-2,3-dioxopropyl]amino]carbonyl]cyclohexyl]-2-furancarboxamide] is an orally bioavailable compound that was synthesized as...
Preclinical pharmacokinetics of TPN729MA, a novel PDE5 inhibitor, and prediction of its human pharmacokinetics using a PBPK model
TPN729MA is a novel selective PDE5 inhibitor currently under clinical development in China for the treatment of erectile dysfunction. In this study we characterized its preclinical pharmacokinetics (PK) and predict its human PK...
Homology Modeling, Molecular Dynamic Simulation and In Silico Screening of Activator for the Intensification of Human Sirtuin Type 1 (SIRT1) By Novel 1, 3, 4-Thiadiazole Derivatives-A Potential Antiaging Approach
Sirtuin type-1(SIRT1) is a regulator of various biosynthetic pathways via activation of peroxisome proliferator-activated receptor-γ and interacting with adenosine-mono-phosphate kinase.