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...
Applications of Mechanistic Modeling and Simulations in Compound and Dosage Forms Selections
Physiologically based pharmacokinetic (PBPK) modeling and simulation techniques have been adopted in the pharmaceutical industry to aid in compound selection and dosage form development in recent years.
Exploring the Feasibility of Biowaiver Extension of BCS Class III Drugs with Site-Specific Absorption Using Gastrointestinal Simulation Technology
The US Food and Drug Administration, World Health Organization and European Medicines Agency have allowed biowaiver for some BCS class III drugs, but shortened the requisite dissolution time of BCS...
The impact of reduced gastric acid secretion on dissolution of salts of weak bases in the fasted upper gastrointestinal lumen: Data in biorelevant media and in human aspirates.
To propose media for simulating the intragastric environment under reduced gastric acid secretion in the fasted state at three levels of simulation of the gastric environment and evaluate their...
Substrate and method dependent inhibition of three ABC-transporters (MDR1, BCRP, and MRP2)
Drug transport and drug-drug interactions (DDI) with human ABC transporters are generally investigated in mammalian cell lines or inverted membrane vesicles from insect cells (Sf9) overexpressing the transporter of interest.
Mechanistic Modelling of Drug-Induced Liver Injury: Investigating the Role of Innate Immune Responses
Drug-induced liver injury (DILI) remains an adverse event of significant concern for drug development and marketed drugs, and the field would benefit from better tools to identify liver liabilities early in development and/or to mitigate potential DILI risk in otherwise promising drugs.
Identification of neuron selective androgen receptor inhibitors
Aim: To identify neuron-selective androgen receptor (AR) signaling inhibitors, which could be useful in the treatment of spinal and bulbar muscular atrophy (SBMA)...
Comparison of oral absorption properties among different bisphosphonates by using a newly developed physiologically based pharmacokinetic model.
Absorption of bisphosphonates（BPs）from the gastrointestinal tract is inhibited by forming a complex combined with multivalent cation in intake foods.
Comparing Dog and Human Intestinal Fluids: Implications on Solubility and Biopharmaceutical Risk Assessment
Despite many documented differences in gut physiology compared to humans, the beagle dog has been successfully used as a preclinical model for assessing the relative bioavailability of dosage forms during formulation development.
Quantitative analysis of lab-to-lab variability in Caco-2 permeability assays
In this study, Caco-2 permeability results from different laboratories were compared. Six different sets of apparent permeability coefficient (Papp) values reported in the literature were...
Mechanistic investigation of the negative food effect of modified release zolpidem
When administered orally as either an immediate or modified release dosage form, zolpidem demonstrates a negative foodeffect, i.e. decrease in Cmax and AUC.
Exploring Canine – Human Differences in Product Performance. Part II: Use of Modeling and Simulation to Explore the Impact of Formulation on Ciprofloxacin In Vivo Absorption and Dissolution in Dogs
This study explored the in vivo performance of three oral ciprofloxacin formulations (oral solution, fast, or slow dissolving tablets) in beagle dogs.
The impact of supersaturation level for oral absorption of BCS class IIb drugs, dipyridamole and ketoconazole, using in vivo predictive dissolution system: Gastrointestinal Simulator (GIS)
The development of formulations and the assessment of oral drug absorption for Biopharmaceutical Classification System (BCS) class IIb drugs is often a difficult issue due to the potential for...
Studies on Core-Shell Nanocapsules of Felodipine: In Vitro-In Vivo Evaluations
The present study aimed for in vitro-in vivo-in silico simulation studies of experimentally designed (32-factorial) Capmul PG-8-cored, Eudragit RSPO-Lutrol F 127 nanocapsules to ferry felodipine using GastroPlus™.
Identification of novel TACE inhibitors compatible with topical application
Targeting the Tumor Necrosis Factor α signalling with antibodies has led to a revolution in the treatment of psoriasis. Locally inhibiting Tumor Necrosis Factor α Converting Enzyme...