Compared with traditional animal methods for toxicity testing, in vitro and in silico methods are widely considered to permit a more cost-effective assessment of chemicals.
Lipophilicity indices derived from the liquid chromatographic behavior observed under bimodal retention conditions (reversed phase/hydrophilic interaction): Application to a representative set of pyridinium oximes
The liquid chromatographic behavior observed under bimodal retention conditions (reversed phase and hydrophilic interaction) offers a new basis for the determination of some derived lipophilicity indices.
Extemporaneously prepared controlled release formulations for accelerating the early phase development of drug candidates
Extemporaneous drug preparations, which are compounded by a pharmacist at a clinical site, are commonly used in early clinical studies to evaluate the performance of drug candidates.
A PPAR-ß/d Agonist is Neuroprotective and Decreases Cognitive Impairment in a Rodent Model of Parkinson’s Disease
Parkinson's disease (PD) is associated with higher risk of cognitive impairment that may lead to memory loss, confusion, and decreased attention span.
The paradox of scientific excellence and the search for productivity in pharmaceutical R&D
Scientific advances in specialty areas are proceeding at a rapid rate, but the research and development enterprise seems unable to take full advantage. Harnessing the steady stream of knowledge and inventions from different...
Simian Virus 40 Large T Antigen Induces IFN-Stimulated Genes through ATR Kinase
Polyomaviruses encode a large T Ag (LT), a multifunctional protein essential for the regulation of both viral and host cell gene expression and productive viral infection.
Use of a systems model of drug-induced liver injury (DILIsym(®)) to elucidate the mechanistic differences between acetaminophen and its less-toxic isomer, AMAP, in mice.
Acetaminophen (APAP) has been used as a probe drug to investigate drug-induced liver injury (DILI). In mice, 3'-hydroxyacetanilide (AMAP), a less-toxic isomer of APAP, has also been studied as a negative control.
From Bench to Humans: Formulation Development of a Poorly Water Soluble Drug to Mitigate Food Effect
This study presents a formulation approach that was shown to mitigate the dramatic food effect observed for a BCS Class II drug. In vitro (dissolution), in vivo (dog), and in silico (GastroPlus®) models...
Application of Physiologically Based Absorption Modeling to Formulation Development of a Low Solubility, Low Permeability Weak Base: Mechanistic Investigation of Food Effect
Physiologically based pharmacokinetic (PBPK) modeling has been broadly used to facilitate drug development, hereby we developed a PBPK model to systematically investigate the...
A Case Study of In Silico Modelling of Ciprofloxacin Hydrochloride / Metallic Compound Interactions
With the development of physiologically based absorption models, there is an increased scientific and regulatory interest in in silico modelling and simulation of drug-drug and drug-food interactions.
Modelling the Absorption of Metformin with Patients Post Gastric Bypass Surgery
Gastric bypass surgery in obesity shortens the length of the small intestine, which can have a significant impact on drug absorption.
Physiologically based pharmacokinetic modeling framework for quantitative prediction of an herb-drug interaction
Herb-drug interaction predictions remain challenging. Physiologically based pharmacokinetic (PBPK) modeling was used to improve prediction accuracy of potential herb-drug interactions...
Differential effects of RUNX2 on the androgen receptor in prostate cancer: synergistic stimulation of a gene set exemplified by SNAI2 and subsequent invasiveness
Changes to androgen signaling during prostate carcinogenesis are associated with both inhibition of cellular differentiation and promotion of malignant phenotypes.
Diaromatic sulfur-containing ‘naphthenic’ acids in process waters
Polar organic compounds found in industrial process waters, particularly those originating from biodegraded petroleum residues, include ‘naphthenic acids’ (NA).
Safety, tolerability, and pharmacokinetic evaluation of single- and multiple-ascending doses of a novel kappa opioid receptor antagonist LY2456302 and drug interaction with ethanol in healthy subjects
Accumulating evidence indicates that selective antagonism of kappa opioid receptors may provide therapeutic benefit in the treatment of major depressive disorder, anxiety disorders, and substance use disorders.
Semi-mechanistic modelling of the analgesic effect of gabapentin in the formalin-induced rat model of experimental pain
The formalin-induced rat model of nociception involves moderate continuous pain. Formalin-induced pain results in a typical repetitive flinching behaviour, which displays a biphasic pattern characterised by peaks of pain.
Imidazole aldoximes effective in assisting butyrylcholinesterase catalysis of organophosphate detoxification
Intoxication by organophosphate (OP) nerve agents and pesticides should be addressed by efficient, quickly deployable countermeasures such as antidotes reactivating acetylcholinesterase or scavenging the parent OP.
Neuroprotective Potential of Peroxisome Proliferator Activated Receptor-a Agonist in Cognitive Impairment in Parkinson’s Disease: Behavioral, Biochemical, and PBPK Profile
Parkinson’s disease (PD) is a common neurodegenerative disorder affecting 1% of the population by the age of 65 years and 4-5% of the population by the age of 85 years.
A mechanistic model of drug-induced liver injury AIDS the interpretation of elevated liver transaminase levels in a phase I clinical trial
Entolimod (CBLB502) is a Toll-like receptor 5 agonist in development as a single-dose countermeasure against total body irradiation.
Differential effects of methoxy group on the interaction of curcuminoids with two major ligand binding sites of human serum albumin
Curcuminoids are a group of compounds with a similar chemical backbone structure but containing different numbers of methoxy groups that have therapeutic potential due to...