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.
Advances in Inhaled Technologies: Understanding the Therapeutic Challenge, Predicting Clinical Performance, and Designing the Optimal Inhaled Product
Inhaled medicines are designed mainly to provide safe and efficacious treatment of respiratory diseases, offering the potential advantages of targeted drug delivery such as reduced onset time and increased therapeutic ratio. However, as a flipside of targeted drug delivery, drug levels in the relevant effect compartment cannot be easily assessed.
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...
Use of Preclinical Dog Studies and Absorption Modeling to Facilitate Late Stage Formulation Bridging for a BCS II Drug Candidate
Formulation changes are common during drug development either due to clinical or manufacturing considerations. These changes especially at later stages of drug development oftentimes raise questions...
Ligand-independent and tissue-selective androgen receptor inhibition by pyrvinium
Pyrvinium pamoate (PP) is a potent noncompetitive inhibitor of the androgen receptor (AR). Using a novel method of target identification, we demonstrate that AR is a...
Evaluation and Optimisation of Current Milrinone Prescribing for the Treatment and Prevention of Low Cardiac Output Syndrome in Paediatric Patients After Open Heart Surgery Using a Physiology-Based Pharmacokinetic Drug-Disease Model
Milrinone is the drug of choice for the treatment and prevention of low cardiac output syndrome (LCOS) in paediatric patients after open heart surgery across Europe.
Linking physiology to toxicity using DILIsym®, a mechanistic mathematical model of drug-induced liver injury
The drug development industry faces multiple challenges in the realization of safe effective drugs.
Small molecule kinase inhibitors approved by the FDA from 2000 to 2011: a systematic review of preclinical ADME data
Fourteen drugs targeting protein kinases have been approved by the United States Food and Drug Administration (FDA) between the years 2000 and 2011.