Search results for "ODR"

Elimination kinetics of the novel prodrug cinazepam possessing psychotropic activity in mice.

2011

Abstract The kinetics of excretion of the novel tranquilizer cinazepam (3-hydroxy-7-bromo-5-( ortho -chlorophenyl)-1,2-dihydro-3H-1,4-benzdiazepin-2-one hemisuccinate (I)) in mice after a single administration and different schemes of multiple administration were determined. Mass balance was studied daily in excretions of mice (feces and urine) for 5-10 days. We observed that monoexponen-tial renal excretion of 14 C-cinazepam and its metabolites predominated with all dosage regimens. Cinazepam and its metabolites were almost fully (> 90%) eliminated in urine and feces over the period of study (5-10 days), which means that no significant accumulation of the drug in the body occurred. The kin…

Renale Wasser- und Elektrolytausscheidung durstender Ratten innerhalb von 32 Stunden nach einmaliger intraven�ser Gabe von Chlormerodrin oder Mersalyl

1959

At the beginning of a period of hunger and thirst, rats received 3 or 4,5 to 5 mg.Hg/kg. as chlormerodrine or mersalyl. The optimal dose of 3mg Hg/kg.as chlormerodrine or 4,5mg. Hg/kg. as mersalyl was effective for more than 32 hours after a single injection.

Wirkungen von Acetazolamid, Chlorothiazid und Chlormerodrin auf die Clearance von Inulin, echtem endogenen Kreatinin, PAH und Harnstoff. Abgrenzung n…

1959

Nonlinear intestinal absorption kinetics of cefuroxime axetil in rats.

1997

Cefuroxime is commercially available for parenteral administration as a sodium salt and for oral administration as cefuroxime axetil, the 1-(acetoxy)ethyl ester of the drug. Cefuroxime axetil is a prodrug of cefuroxime and has little, if any, antibacterial activity until hydrolyzed in vivo to cefuroxime. In this study, the absorption of cefuroxime axetil in the small intestines of anesthetized rats was investigated in situ, by perfusion at four concentrations (11.8, 5, 118 and 200 microM). Oral absorption of cefuroxime axetil can apparently be described as a specialized transport mechanism which obeys Michaelis-Menten kinetics. Parameters characterizing absorption of prodrug in free solutio…

Maintenance of glutathione levels and its importance in epigenetic regulation.

2014

Glutathione (GSH) is present in almost all cell types playing an important function in organisms. It is the main antioxidant in many cell types and it also regulates the function of proteins, including transcription factors (reviewed in Pallardo et al., 2009; Markovic et al., 2010; Garcia-Gimenez et al., 2013a). Over recent years, growing evidence has suggested a link between GSH metabolism and the control of epigenetic mechanisms. Epigenetics is defined as the mitotically/meiotically heritable changes in gene expression that are not due to changes in the primary DNA sequence. This link between GSH and epigenetics occurs at different levels. Hence, GSH can affect DNA and histone methylation…

Discovery of SI 1/20 and SI 1/22 as Mutual Prodrugs of 5-Fluorouracil and Imidazole-Based Heme Oxygenase 1 Inhibitor with Improved Cytotoxicity in DU…

2023

: In this work, we extend the concept of 5-fluorouracil/heme oxygenase 1 (5-FU/HO-1) inhibitor hybrid as an effective strategy for enhancing 5-FU-based anticancer therapies. For this purpose, we designed and synthesized new mutual prodrugs, named SI 1/20 and SI 1/22, in which the two active parent drugs (i. e., 5-FU and an imidazole-based HO-1 inhibitor) were connected through an easily cleavable succinic linker. Experimental hydrolysis rate, and in silico ADMET predictions were indicative of good drug-likeness and pharmacokinetic properties. Novel hybrids significantly reduced the viability of prostate DU145 cancer cells compared to the parent compounds 5-FU and HO-1 inhibitor administered…

Formation of N-methylnicotinamide in the brain from a dihydropyridine-type prodrug

1999

The enhancement of brain choline levels is a possible therapeutic option in neurodegenerative diseases; however, brain choline levels are held within narrow limits by homeostatic mechanisms including the rapid clearance of excess choline from the brain. The present study tests whether N-methylnicotinamide (NMN), an inhibitor of the outward transport of choline from the brain, can elevate brain choline levels in vivo. As NMN does not cross the blood-brain barrier, we synthesized and administered the brain-permeable prodrug, 1,4-dihydro-N-methyl-nicotinamide (DNMN), and tested its effect on the levels of NMN and choline in brain extracellular fluid, using the microdialysis procedure. Administ…

The Philippines 2017 : Duterte-led Authoritarian Populism and Its Liberal-Democratic Roots

2017

Philippine President Rodrigo Duterte led a phenomenal campaign to win the 2016 national election. During his first two years in power Duterte has become the protagonist and exemplar of a key new development – the social formation of a regime of authoritarian populism. Based on an analysis of news reports, public debates, survey results, and official policy documents from 2017, the article examines various features of this emergent regime and then illuminates the historical-institutional mechanisms that brought it about. The inquiry is predicated on an understanding that the old EDSA Republic’s liberal-democratic regime has been marked by intractable socio-economic crises since its installat…

Quantum spectral curve for arbitrary state/operator in AdS$_5$/CFT$_4$

2015

We give a derivation of quantum spectral curve (QSC) - a finite set of Riemann-Hilbert equations for exact spectrum of planar N=4 SYM theory proposed in our recent paper Phys.Rev.Lett. 112 (2014). We also generalize this construction to all local single trace operators of the theory, in contrast to the TBA-like approaches worked out only for a limited class of states. We reveal a rich algebraic and analytic structure of the QSC in terms of a so called Q-system -- a finite set of Baxter-like Q-functions. This new point of view on the finite size spectral problem is shown to be completely compatible, though in a far from trivial way, with already known exact equations (analytic Y-system/TBA, …

Classical and Quantum Nonultralocal Systems on the Lattice

1997

We classify nonultralocal Poisson brackets for 1-dimensional lattice systems and describe the corresponding regularizations of the Poisson bracket relations for the monodromy matrix. A nonultralocal quantum algebras on the lattices for these systems are constructed. For some class of such algebras an ultralocalization procedure is proposed. The technique of the modified Bethe-Anzatz for these algebras is developed and is applied to the nonlinear sigma model problem.