BMS-914392 is a tricyclic pyranoquinoline BCS class 2 weak base that demonstrates high solubility in low pH environments. Initial clinical studies indicated that rapid release of high dose BMS-914392 led to...
Analysis of Intra- and Intersubject Variability in Oral Drug Absorption in Human Bioequivalence Studies of 113 Generic Products
In this study, the data of 113 human bioequivalence (BE) studies of immediate release (IR) formulations of 74 active pharmaceutical ingredients (APIs) conducted at Sawai Pharmaceutical Co., Ltd., was...
Radiosynthesis and evaluation of N-(3,4-dimethylisoxazol-5-yl)piperazine-4-[4-(4-fluorophenyl)thiazol-2-yl]-1-[11C]carboxamide for in vivo positron emission tomography imaging of fatty acid amide hydrolase in brain
We developed a novel positron emission tomography (PET) radiotracer N-(3,4-dimethylisoxazol-5-yl)piperazine-4-[4-(4-fluorophenyl)thiazol-2-yl]-1-[11C]carboxamide ([11C]DPFC, [11C]1) for in vivo...
Identification of a major radiometabolite of [11C]PBB3
[11C]PBB3 is a clinically used positron emission tomography (PET) probe for in vivo imaging of tau pathology in the brain. Our previous study showed that [11C]PBB3 was rapidly decomposed to...
Effect of SI-591, a new class of cathepsin K inhibitor with peptidomimetic structure, on bone metabolism in vitro and in vivo
SI-591[N-[1-[[[(1S)-3-[[(3S)-hexahydro-2-oxo-1H-azepin-3-yl]amino]-1-(1-methylethyl)-2,3-dioxopropyl]amino]carbonyl]cyclohexyl]-2-furancarboxamide] is an orally bioavailable compound that was synthesized as...
Preclinical pharmacokinetics of TPN729MA, a novel PDE5 inhibitor, and prediction of its human pharmacokinetics using a PBPK model
TPN729MA is a novel selective PDE5 inhibitor currently under clinical development in China for the treatment of erectile dysfunction. In this study we characterized its preclinical pharmacokinetics (PK) and predict its human PK...
Homology Modeling, Molecular Dynamic Simulation and In Silico Screening of Activator for the Intensification of Human Sirtuin Type 1 (SIRT1) By Novel 1, 3, 4-Thiadiazole Derivatives-A Potential Antiaging Approach
Sirtuin type-1(SIRT1) is a regulator of various biosynthetic pathways via activation of peroxisome proliferator-activated receptor-γ and interacting with adenosine-mono-phosphate kinase.
In vitro-in vivo correlation of parenteral risperidone polymeric microspheres
The objective of the present study was to determine whether an in vitro-in vivo correlation (IVIVC) can be established for polymeric microspheres that are equivalent in formulation composition but...
Physicochemical Understanding of Solubility and Supersaturation for the Enhancement of the Oral Absorbability of Poorly Soluble Drugs
Many new chemical entities are developed as oral solid form drugs such as tablets and capsules due to their patient-friendliness.
An Update of the Brazilian Regulatory Bioequivalence Recommendations for Approval of Generic Topical Dermatological Drug Products
This note aims to clarify the Brazilian regulatory bioequivalence recommendations for approval of generic topical dermatological drug products, since the legal framework of the "Brazilian Health Surveillance Agency" (ANVISA) is only available in Portuguese.
Assessment of in silico models for acute aquatic toxicity towards fish under REACH regulation
We evaluated the performance of eight QSAR in silico modelling packages (ACD/ToxSuite™, ADMET Predictor™, DEMETRA, ECOSAR, TerraQSAR™, Toxicity Estimation Software Tool, TOPKAT™ and VEGA) for...
Tools for early prediction of drug loading in lipid-based formulations
Identification of the usefulness of lipid-based formulations (LBFs) for delivery of poorly water-soluble drugs is at date mainly experimentally based.
Novel derivatives of nitro-substituted salicylic acids: Synthesis, antimicrobial activity and cytotoxicity
Inspired by the high antituberculous activity of novel nitro-substituted derivatives and based on promising predicted ADMET properties we have synthesized a series of 33 salicylanilides containing...
Benzazaborinines as novel bioisosteric replacements of naphthalene: propranolol as an example
Two benzazaborinine analogues of propranolol were synthesized and extensively profiled in vitro and in vivo.
Physical Stability of Drugs after Storage Above and Below the Glass Transition Temperature: Relationship to Glass-Forming Ability
Amorphous materials are inherently unstable and tend to crystallize upon storage. In this study, we investigated the extent to which the physical stability and inherent crystallization tendency of drugs are related...
Pharmacologic Activities of 3′- Hydroxypterostilbene: Cytotoxic, Anti-Oxidant, Anti-Adipogenic, Anti-Inflammatory, Histone Deacetylase and Sirtuin 1 Inhibitory Activity
Delineate the selected pharmacodynamics of a naturally occurring stilbene 3’-Hydroxypterostilbene.
The evolution and future of environmental partition coefficients
Partition or distribution coefficients (and increasingly referred to as partition ratios) are widely used in environmental science to relate the concentration of a chemical solute in one phase to that in a...
Physiologically Based Pharmacokinetic (PBPK) Modeling and Simulation Approaches: A systematic review of published models, applications and model verification
Modeling and simulation of drug disposition has emerged as an important tool in drug development, clinical study design and regulatory review, and the number of physiologically based pharmacokinetic (PBPK) modeling...
Comparison of Deconvolution-Based and Absorption Modeling IVIVC for Extended Release Formulations of a BCS III Drug Development Candidate
In vitro-in vivo correlations (IVIVC) are predictive mathematical models describing the relationship between dissolution and plasma concentration for a given drug compound.
Assessment of In Vivo Clinical Product Performance of a Weak Basic Drug by Integration of In Vitro Dissolution Tests and Physiologically Based Absorption Modeling
Effective integration of in vitro tests and absorption modeling can greatly improve our capability in understanding, comparing, and predicting in vivo performances of clinical drug products.