A 2024 Update on US FDA Implementation of Partial Area Under the Curve Into Bioavailability and Bioequivalence Assessments.

Comparisons of maximum drug concentration (C) and total area under the concentration vs. time curve (AUC) may be inadequate for bioavailability (BA)/bioequivalence (BE) assessments in cases where the shape of the pharmacokinetic (PK) profile of a drug impacts the clinical performance. In such cases, partial area under the concentration vs.

A 3D Model of the Human Lung Airway for Evaluating Permeability of Inhaled Drugs.

Current in vitro cell-based methods, relying on single cell types, have structural and functional limitations in determining lung drug permeability, which is a contributing factor affecting both local and systemic drug levels. To address this issue, we investigated a 3D human lung airway model generated using a cell culture insert, wherein primary human lung epithelial and endothelial cells were cocultured at an air-liquid interface (ALI). To ensure that the cell culture mimics the physiological and functional characteristics of airway tissue, the model was characterized by evaluating several parameters such as cellular confluency, ciliation, tight junctions, mucus-layer formation, transepithelial electrical resistance, and barrier function through assaying fluorescein isothiocyanate-dextran permeability.

Unsupervised Dimensionality Reduction Techniques for the Assessment of ASD Biomarkers.

Autism Spectrum Disorder (ASD) encompasses a range of developmental disabilities marked by differences in social functioning, cognition, and behavior. Both genetic and environmental factors are known to contribute to ASD, yet the exact etiological factors remain unclear. Developing integrative models to explore the effects of gene expression on behavioral and cognitive traits attributed to ASD can uncover environmental and genetic interactions.

Epigenetic age acceleration predicts subject-specific white matter degeneration in the human brain.

Epigenetic clocks provide powerful tools for estimating health and lifespan but their ability to predict brain degeneration and neuronal damage during the aging process is unknown. In this study, we use GrimAge, an epigenetic clock correlated to several blood plasma proteins, to longitudinally investigate brain cellular microstructure in axonal white matter from a cohort of healthy aging individuals. A specific focus was made on white matter hyperintensities, a visible neurological manifestation of small vessel disease, and the axonal pathways throughout each individual's brain affected by their unique white matter hyperintensity location and volume.

Exploration of the potential impact of batch-to-batch variability on the establishment of pharmacokinetic bioequivalence for inhalation powder drug products.

Batch-to-batch variability in inhalation powder has been identified as a potential challenge in the development of generic versions. This study explored the impact of batch-to-batch variability on the probability of establishing pharmacokinetic (PK) bioequivalence (BE) in a two-sequence, two-period (2 × 2) crossover study. A model-based parametric simulation approach was employed, incorporating batch-to-batch variability through the relative bioavailability (RBA) ratio.