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An evaluation of the CYP2D6 and CYP3A4 inhibition potential of metoprolol metabolites and their contribution to drug–drug and drug–herb interaction by LC‐ESI/MS/MS
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Roshan M. Borkar Murali Mohan Bhandi Ajay P. Dubey V. Ganga Reddy Prashanth Komirishetty Prajwal P. Nandekar Abhay T. Sangamwar Ahmed Kamal Sanjay K. Banerjee R. Srinivas 《Biomedical chromatography : BMC》2016,30(10):1556-1572
The aim of the present study was to evaluate the contribution of metabolites to drug–drug interaction and drug–herb interaction using the inhibition of CYP2D6 and CYP3A4 by metoprolol (MET) and its metabolites. The peak concentrations of unbound plasma concentration of MET, α‐hydroxy metoprolol (HM), O‐desmethyl metoprolol (ODM) and N‐desisopropyl metoprolol (DIM) were 90.37 ± 2.69, 33.32 ± 1.92, 16.93 ± 1.70 and 7.96 ± 0.94 ng/mL, respectively. The metabolites identified, HM and ODM, had a ratio of metabolic area under the concentration–time curve (AUC) to parent AUC of ≥0.25 when either total or unbound concentration of metabolite was considered. In vitro CYP2D6 and CYP3A4 inhibition by MET, HM and ODM study revealed that MET, HM and ODM were not inhibitors of CYP3A4‐catalyzed midazolam metabolism and CYP2D6‐catalyzed dextromethorphan metabolism. However, DIM only met the criteria of >10% of the total drug related material and <25% of the parent using unbound concentrations. If CYP inhibition testing is solely based on metabolite exposure, DIM metabolite would probably not be considered. However, the present study has demonstrated that DIM contributes significantly to in vitro drug–drug interaction. Copyright © 2016 John Wiley & Sons, Ltd. 相似文献
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C. V. Chaudhari K. A. Dubey Y. K. Bhardwaj S. Sabharwal 《Journal of Macromolecular Science: Physics》2013,52(5):839-859
Different compositions of SBR/EPDM 50:50 blends containing multiple-walled carbon nanotubes (MWNT) as nanoparticulate fillers (0.5%–10%) were evaluated for radiation sensitivity and solvent permeability. The efficiency of radiation ***cross-linking was analyzed by gel-content and Charlesby–Pinner parameter measurements. ***Gamma-radiation-induced cross-linking extent was found to increase with radiation dose and MWNT concentration, which was reflected in different extents of swelling. Rigorous analysis of swelling and diffusion data, on the basis of the transport exponent (n) values and diffusion/relaxation rate indicated anomalous diffusion behavior for most of the nanocomposites. The swelling extent in different solvents was found to be a function of polymer-solvent interaction as well as stearic hindrance due to the structure/size of the solvent molecules. Polymer-filler interaction investigated by a Kraus plot indicated high reinforcement of the SBR/EPDM matrix on MWNT addition. There was no significant change in surface energy or hydrophilicity of the SBR/EPDM matrix on introduction of MWNT into it. 相似文献
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A. Indrasena Sd. Riyaz Prema L. Mallipeddi P. Padmaja B. Sridhar P.K. Dubey 《Tetrahedron letters》2014
A series of indolylidinepyrazolones were synthesized using a simple, green, and effective route and evaluated as anti-bacterial agents. The compounds were further studied via structure-guided docking study. One of the compounds exhibiting H-bonding interactions with conserved residue Arg144 turned out to be the most potent compound of the series. The minimum inhibitory concentration values ranged from 50 to 25 μg/mL against Staphylococcus aureus in their anti microbial evaluation. 相似文献
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The first example of pyrrolidine‐based room‐temperature chiral ionic liquids using 2‐aminobutanol as chiral auxiliary is described. 相似文献
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Co‐polymeric hydrogels consisting of N‐vinyl‐2‐pyrrolidone (NVP) and acrylic acid (AAc) were synthesized and evaluated for release of a model drug, i.e., vitamin B12. Release studies in simulated gastric fluid (pH 1.2) and intestinal fluid (pH 7.4), at 37°C, showed the hydrogels to be pH sensitive. An in vitro release study by ‘traditional dissolution test’ (TDT) showed that percent drug released from the hydrogel was nearly 8.6±2.1 and 83.2±4.8 in the media of pH 1.2 and 6.8, respectively. However, in order to incorporate in vivo GI conditions such as acidic pH and high water content in the stomach, low water content and the presence of a semi–solid mass in the large intestine, a new test model, called flow through diffusion cell (FTDC) was also used. The two approaches yielded almost different release profiles. The gels were characterized by thermogravimetric analysis and FTIR spectroscopy. 相似文献
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Trichloroisocyanuric acid–KF afforded dialkylfluorophosphates from dialkylphosphites at room temperature through a facile electrophilic–nucleophilic metathesis. 相似文献