Population Pharmacokinetic Modeling and Simulation for Dose Optimization of GB-5001, a Long-Acting Intramuscular Injection of Donepezil, in Healthy Participants.

Introduction: GB-5001 is an intramuscular (IM) formulation of donepezil under development for the treatment of Alzheimer's disease. The objective of this study was to develop a population pharmacokinetic (PK) model for donepezil in both IM and oral formulations, and to optimize the IM dosage of GB-5001 using bioequivalence (BE) simulation.

Methods: A population PK model of donepezil was developed using NONMEM.

How to lead on carbon neutrality through sustainable development: A perspective on renewable energy, Information and Communication Technology (ICT), and logistics networks.

In the face of intensifying climate change-induced environmental problems, understanding the causal relationship between carbon dioxide (CO2) emissions and socioeconomic factors is crucial for achieving sustainable development. This study investigates how the causal relationships between renewable energy, information and communication technology (ICT), logistics networks, economic growth, industrialization, and energy intensity impact sustainable development using a panel dataset drawn from 104 countries and covering 2006 to 2019. Methodologically, panel unit root, panel co-integration, and Granger causality tests are employed as robust econometric techniques.

The dynamic relationship between industrialization, urbanization, CO emissions, and transportation modes in Korea: empirical evidence from maritime and air transport.

This study investigates the causal relationship between logistics efficiency and factors affecting the logistics environment, such as industrialization, urbanization, and CO2 emissions. With the expectation that logistics efficiency will contribute to economic growth and enhance country competitiveness in the near future, it is necessary to confirm the impact of each factor on different transportation modes, such as maritime and air transport. To this end, this study identifies causal relationships between the factors affecting the logistics environment and specific modes of transportation using data from 2010 to 2018.

Donepezil ameliorates Aβ pathology but not tau pathology in 5xFAD mice.

The cholinesterase inhibitor donepezil is used to improve Aβ pathology and cognitive function in patients with Alzheimer's disease (AD). However, the impact of donepezil on tau pathology is unclear. Thus, we examined the effects of donepezil on Aβ and tau pathology in 5xFAD mice (a model of AD) in this study.

Donepezil Regulates LPS and Aβ-Stimulated Neuroinflammation through MAPK/NLRP3 Inflammasome/STAT3 Signaling.

The acetylcholinesterase inhibitors donepezil and rivastigmine have been used as therapeutic drugs for Alzheimer's disease (AD), but their effects on LPS- and Aβ-induced neuroinflammatory responses and the underlying molecular pathways have not been studied in detail in vitro and in vivo. In the present study, we found that 10 or 50 μM donepezil significantly decreased the LPS-induced increases in the mRNA levels of a number of proinflammatory cytokines in BV2 microglial cells, whereas 50 μM rivastigmine significantly diminished only LPS-stimulated IL-6 mRNA levels. In subsequent experiments in primary astrocytes, donepezil suppressed only LPS-stimulated iNOS mRNA levels.

Pharmacokinetic properties and effects of PT302 after repeated oral glucose loading tests in a dose-escalating study.

Background: PT302 is a sustained-release exenatide under clinical development for the treatment of type 2 diabetes mellitus.

Objective: The aim of this study was to evaluate the pharmacokinetic properties, pharmacodynamic properties, and tolerability of PT302 after a single subcutaneous injection in healthy individuals.

Methods: A dose-block randomized, double-blind, placebo-controlled, dose-escalating study (0.

Long-acting injectable formulations of antipsychotic drugs for the treatment of schizophrenia.

Antipsychotic drugs have been used to treat patients with schizophrenia and other psychotic disorders. Long-acting injectable antipsychotic drugs are useful for improving medication compliance with a better therapeutic option to treat patients who lack insight or adhere poorly to oral medication. Several long-acting injectable antipsychotic drugs are clinically available.

Roles of human liver cytochrome P450 3A4 and 1A2 enzymes in the oxidation of myristicin.

The aim of this work was to identify the form(s) of human liver cytochrome P450 (CYP) involved in the hepatic transformation of myristicin to its major metabolite, 5-allyl-1-methoxy-2,3-dihydroxybenzene. When microsomes prepared from different human liver samples were compared, the activity of 5-allyl-1-methoxy-2,3-dihydroxybenzene formation was well correlated (r(2)=0.87) with nifedipine oxidation (a marker of CYP3A4).

In vitro metabolism of a novel phosphodiesterase-5 inhibitor DA-8159 in rat liver preparations using liquid chromatography/electrospray mass spectrometry.

The in vitro metabolism of a new erectogenic, DA-8159, has been studied by LC with UV detection and on-line LC-electrospray mass spectrometry using rat hepatic microsomal incubation and rat liver perfusion. Both rat liver microsomal incubation of DA-8159 in the presence of NADPH and single-pass liver perfusion of DA-8159 resulted in the formation of three metabolites (M1-3). M1 was tentatively identified as hydroxy-DA-8159.

LC-MS/MS identification of in vitro metabolites of a new H+/K+ ATPase inhibitor, KR-60436 produced by rat and human liver microsomes.

The metabolism of a new H+/K+ ATPase inhibitor, KR-60436 [1-(4-methoxy-2-methyl-phenyl)-4-[(2-hydroxyethyl)amino]-6-trifluoromethoxy-2,3-dihydropyrrolo[3,2-c]quinoline] has been studied by LC-electrospray mass spectrometry. In vitro incubation of KR-60436 with rat and human liver microsomes in the presence of NADPH produced seven metabolites (M1-M7). M3-M6 were identified as O-demethyl-KR-60436, O-demethyl-pyrrole-KR-60436, N-dehydroxyethyl-KR-60436 and pyrrole-KR-60436, respectively, based on LC/MS/MS analysis with authentic standards.

Analysis of tofisopam in human serum by column-switching semi-micro high-performance liquid chromatography and evaluation of tofisopam bioequivalency.

A rapid and sensitive column-switching semi-micro HPLC method is described for the direct analysis of tofisopam in human serum. The sample (100 microL) was directly injected onto the precolumn (Capcell Pak MF Ph-1), where unretained proteins were eluted to waste. Tofisopam was then eluted into an enrichment column using 13% acetonitrile in 50 mM phosphate buffer (pH 7.