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...
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.