The objectives of this study were to characterize the pharmacokinetics (PK) of LY2510924, a potent peptide antagonist of the CXCR4 receptor, after subcutaneous administration in patients with...
Discovery of Resistance Pathways to Fibroblast Growth Factor Receptor inhibition in Bladder Cancer
Background Aberrant fibroblast growth factor receptor (FGFR) signaling drives the growth of many bladder cancers. NVP-BGJ398 is a small molecule with potent inhibitory...
Biorelevant Dissolution Models for a Weak Base To Facilitate Formulation Development and Overcome Reduced Bioavailability Caused by Hypochlordyria or Achlorhydria.
In this study, two dissolution models were developed to achieve in vitro–in vivo relationship for immediate release formulations of Compound-A, a poorly soluble weak base with pH-dependent...
Synthesis, antioxidant, antifungal, molecular docking and ADMET studies of some thiazolyl hydrazones
Some thiazolyl hydrazones were synthesized by one pot reaction of thiophene-2-carbaldehyde or 2, 4-dichlorobenzaldehyde, thiosemicarbazide and various phenacyl bromides which were preliminarily...
An Intuitive Approach for Predicting Potential Human Health Risk with the Tox21 10k Library
In vitro-in vivo extrapolation (IVIVE) analyses translating high-throughput screening (HTS) data to human relevance have been limited.
Mathematical model reveals role of nucleotide signaling in airway surface liquid homeostasis and its dysregulation in cystic fibrosis
Mucociliary clearance is composed of three components (i.e., mucin secretion, airway surface hydration, and ciliary-activity) which function coordinately to clear inhaled microbes and other foreign particles from airway surfaces.
In Silico Absorption Analysis of Valacyclovir in Wildtype and Pept1 Knockout Mice Following Oral Dose Escalation
We developed simulation and modeling methods to predict the in vivo pharmacokinetic profiles of acyclovir, following escalating oral doses of valacyclovir, in wildtype and Pept1knockout mice.
Lipophilic salts of poorly soluble compounds to enable high-dose lipidic SEDDS formulations in drug discovery
Self-emulsifying drug delivery systems (SEDDS) have been used to solubilize poorly water-soluble drugs to improve exposure in high-dose pharmacokinetic (PK) and toxicokinetic (TK) studies.
In silico prediction of skin metabolism and its implication in toxicity assessment
Skin, being the largest organ of the body, represents an important route of exposure, not only for the abundance of chemicals present in the environment, but also for...
The Use of In Vitro and In Silico Technologies for Predicting Human Pharmacology and Toxicology of Carfentanil
Carfentanil is an ultra-potent opioid of public health and chemical weapons defense concern.
Integrating in vitro, modeling, and in vivo approaches to investigate warfarin bioequivalence
We demonstrate the use of modeling and simulation to investigate bioequivalence concerns raised about generic warfarin products.
Identification and characterisation of a salt form of Danirixin with reduced pharmacokinetic variability in patient populations
The natural variability of gastric pH or gastric acid reducing medications can result in lower and more variable clinical pharmacokinetics for basic compounds in patient populations.
Oral product input to the GI tract: GIS an oral product performance technology
The patient receives a pharmaceutical product, not a drug.
Calcium Phosphate Particles as Pulmonary Delivery System for Interferon-α in Mice
Systemically administered interferons are rapidly cleared from the circulation thus requiring frequent dosing to maintain the therapeutic levels of circulating interferon.
Utility of Physiologically Based Pharmacokinetic Absorption Modeling to Predict the Impact of Salt-to-Base Conversion on Prasugrel HCl Product Bioequivalence in the Presence of Proton Pump Inhibitors
Prasugrel HCl may convert to prasugrel base during manufacturing or storage. It was reported that formulations with different ratios of salt to base were bioequivalent in healthy subjects...
Prediction of Intracellular Exposure Bridges the Gap Between Target- and Cell-Based Drug Discovery
Inadequate target exposure is a major cause of high attrition in drug discovery. Here, we show that a label-free method for quantifying the intracellular bioavailability (Fic) of drug molecules…
Synthesis and pharmacodynamics of ibuprofen-1-acetoxyethyl ester
Ibuprofen(IBU) and its derivatives are widely used in treating many diseases, such as depression, glomerulonephritis, fever caused by common cold or influenza, and rheumatoid arthritis.
In vitro–in vivo and pharmacokinetic evaluation of solid lipid nanoparticles of furosemide using Gastroplus™
In this work, we conducted pharmacokinetic studies and established the in vitro and in vivo correlation (IVIVC) of furosemide (FRS) loaded solid lipid nanoparticles (FSLN).
Prediction of efficacy for conversion from adjunctive therapy to monotherapy with eslicarbazepine acetate 800 mg once daily for partial-onset epilepsy.
Eslicarbazepine acetate (ESL) is a once-daily (QD) oral antiepileptic drug (AED) indicated for partial-onset seizures (POS). Clinical studies of gradual conversion to ESL 1,200 and 1,600 mg QD...