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31.
32.
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 下载免费PDF全文
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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Priyanka Lohar Manish Kumar Sharma Amit Kumar Sahu Rajeswari Rathod Pinaki Sengupta 《Biomedical chromatography : BMC》2019,33(12)
The combination of acebrophylline (ABP), levocetirizine (LCZ) and pranlukast (PRN) is used to treat allergic rhinitis, asthma, hay‐fever and other conditions where patients experience difficulty in breathing. This study was carried out with the aim of developing and validating a reverse‐phase high‐performance liquid chromatographic bioanalytical method to simultaneously quantitate ABP, LCZ and PRN in rat plasma. The objective also includes determination of the pharmacokinetic interaction of these three drugs after administration via the oral route after individual and combination treatment in rat. Optimum resolution between the analytes was observed with a C18 Kinetex column (250 mm × 4.6 mm × 5 μm). The chromatography was performed in a gradient elution mode with a 1 mL/min flow rate. The calibration curves were linear over the concentration range of 100–1600 ng/mL. The intra‐ and inter‐day precision and accuracy were found to be within acceptable limits as specified in US Food and Drug Administration guideline for bioanalytical method validation. The analytes were stable on the bench‐top (8 h), after three freeze–thaw cycles, in the autosampler (8 h) and as a dry extract (?80°C for 48 h). The statistical results of the pharmacokinetic study in Sprague–Dawley rats showed a significant change in pharmacokinetic parameters for PRN upon co‐administration of the three drugs. 相似文献
35.
Poonam Sharma D. K. Kanchan Nirali Gondaliya Meenakshi Pant Manish S. Jayswal 《Ionics》2013,19(2):301-307
In this paper, the electrical conductivity and relaxation studies in two different temperature regions (T?<?T m and T?>?T m) on plasticized PEO–PMMA blend polymer electrolyte system with AgNO3 salt are reported. The polymer electrolyte system has been prepared by solution cast technique and characterized by X-ray diffraction and differential scanning calorimetry. The conduction and relaxation processes at various temperatures have been investigated in the framework of modulus formalism. The distribution of relaxation times is discussed using Argand plot. Variation in ionic conductivity of polymer blends is discussed with the increase of PEO as well as with temperature. 相似文献
36.
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
37.
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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Dr. Chandan Kumar Karan Sourav Mallick Prof. Dr. C. Retna Raj Prof. Dr. Manish Bhattacharjee 《Chemistry (Weinheim an der Bergstrasse, Germany)》2019,25(65):14775-14779
A zinc containing metal–organic gel (Zn-MOG) with embedded free ions, which exhibits self-healing properties, has been synthesized for application in supercapacitors. The activated carbon-based flexible supercapacitor device with the MOG electrolyte has a broad potential window of 2.1 V, with high retention of specific capacitance compared to the traditional polyvinyl alcohol (PVA)-based gel. The Zn-MOG does not require an additional electrolyte. The sodium and sulphate ions embedded in the MOG are sufficient enough for the charge storage. 相似文献
40.
GPU‐accelerated direct numerical simulations of decaying compressible turbulence employing a GKM‐based solver 下载免费PDF全文
Gas Kinetic Method‐based flow solvers have become popular in recent years owing to their robustness in simulating high Mach number compressible flows. We evaluate the performance of the newly developed analytical gas kinetic method (AGKM) by Xuan et al. in performing direct numerical simulation of canonical compressible turbulent flow on graphical processing unit (GPU)s. We find that for a range of turbulent Mach numbers, AGKM results shows excellent agreement with high order accurate results obtained with traditional Navier–Stokes solvers in terms of key turbulence statistics. Further, AGKM is found to be more efficient as compared with the traditional gas kinetic method for GPU implementation. We present a brief overview of the optimizations performed on NVIDIA K20 GPU and show that GPU optimizations boost the speedup up‐to 40x as compared with single core CPU computations. Hence, AGKM can be used as an efficient method for performing fast and accurate direct numerical simulations of compressible turbulent flows on simple GPU‐based workstations. Copyright © 2016 John Wiley & Sons, Ltd. 相似文献