Partial AUCs in Long-Acting Injectables: Rationale, Challenges, Variability, Usefulness, and Clinical Relevance.

Regulatory authorities typically require bioequivalence to be demonstrated by comparing pharmacokinetic parameters like area under the plasma concentration-time curve (AUC) and maximum plasma concentration (C). Because in certain cases, AUC and C alone may not be adequate to identify formulation differences in early and/or late segments of the dosing interval, partial AUCs (pAUCs) have been proposed as additional metrics to evaluate bioequivalence. Even though cut-off points for pAUCs are usually decided based on clinical relevance, the identification of the correct cut-off range remains elusive in many other cases and tends to contribute to increased pAUC estimate variabilities.

Pharmacokinetic/Pharmacodynamic Determination of Systemic MIC Breakpoints for Intermittent, Extended, and Continuous Infusion Dosage Regimens of Mecillinam.

Intravenous mecillinam has been used for the treatment of urosepsis at several dosing regimens, including a dose of 1,000 mg three times a day (TID). In the current pharmacokinetic/pharmacodynamic (PK/PD) study, we analyzed intermittent, extended, and continuous infusion regimens of mecillinam to provide dosage recommendations to treat infections caused by exhibiting relatively higher mecillinam MICs than the wild-type strains. Monte Carlo simulation studies indicated that regimens of 1,000 mg TID and 1,000 to 1,200 mg four times a day (QID) are efficacious against wild-type and extended-spectrum β-lactamase-producing , respectively.

Hydrophobicity of surface-immobilised molecules influences architectures formed via interfacial self-assembly of nucleoside-based gelators.

Surface-mediated self-assembly has potential in biomaterial development but underlying rules governing surface-gelator interactions are poorly understood. Here, we correlate surface properties with structural characterization data of nucleoside-based gels obtained by GISAXS and GIWAXS and find that hydrophobicity descriptors (log P, polar surface area, aromaticity) are key predictors for the gel structures formed.

Supramolecular Nucleoside-Based Gel: Molecular Dynamics Simulation and Characterization of Its Nanoarchitecture and Self-Assembly Mechanism.

Among the diversity of existing supramolecular hydrogels, nucleic acid-based hydrogels are of particular interest for potential drug delivery and tissue engineering applications because of their inherent biocompatibility. Hydrogel performance is directly related to the nanostructure and the self-assembly mechanism of the material, an aspect that is not well-understood for nucleic acid-based hydrogels in general and has not yet been explored for cytosine-based hydrogels in particular. Herein, we use a broad range of experimental characterization techniques along with molecular dynamics (MD) simulation to demonstrate the complementarity and applicability of both approaches for nucleic acid-based gelators in general and propose the self-assembly mechanism for a novel supramolecular gelator, N-octanoyl-2'-deoxycytidine.

Surface-directed modulation of supramolecular gel properties.

Supramolecular materials are widely studied and used for a variety of applications; in most applications, these materials are in contact with surfaces of other materials. Whilst much focus has been placed on elucidating factors that affect supramolecular material properties, the influence of the material surface on gel formation is poorly characterised. Here, we demonstrate that surface properties directly affect the fibre architecture and mechanical properties of self-assembled cytidine based gel films.