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1.
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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The constant stepsize analog of Gelfand–Mitter type discrete-time stochastic recursive algorithms is shown to track an associated stochastic differential equation in the strong sense, i.e., with respect to an appropriate divergence measure. 相似文献
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V. S. Borkar 《Journal of Optimization Theory and Applications》1990,66(2):289-309
The Kumar-Becker-Lin scheme introduces a slowly vanishing cost bias in the parameter estimation part of self-tuning control in order to improve its performance. This paper establishes the a.s. optimality of a variant of this scheme for Markov chains on a countable state space when the action space is compact metric and the parameter space is a compact subset ofR
m
. 相似文献
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Santosh Ramdas Borkar Naveen Bokolia Indrapal Singh Aidhen Inshad Ali Khan 《Tetrahedron: Asymmetry》2017,28(1):186-195
A series of threo- and erythro-configured open-chain trihydroxy ketones was synthesized starting from l- and d-ascorbic acid respectively as the starting material, through the use of Grignard reactions for the requisite CC bond formations. The lipophilic ketones were screened against Mycobacteriumtuberculosis for anti-proliferative activity. The lipophilic ketones with tetradecyl alkyl side chains were found to be moderately active against cell proliferation. 相似文献
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Homoallylic substrates such as (E)-6-arylhex-3-enyl alcohols, N-tosylamides, and thiols undergo smooth cross-coupling with various aldehydes in the presence of 10 mol % Sc(OTf)(3) and 30 mol % TsOH to afford the trans-fused hexahydro-1H-benzo[f]isochromenes, N-tosyloctahydrobenzo[f]isoquinolines, and hexahydro-1H-benzo[f]isothiochromenes, respectively. However, the cross-coupling of (Z)-olefins such as 6-arylhex-3-enyl alcohols, N-tosylamides, and thiols with aldehydes affords the corresponding hexahydro-1H-benzo[f]isochromenes, N-tosyloctahydrobenzo[f]isoquinolines, and hexahydro-1H-benzo[f]isothiochromenes with complete cis selectivity via intramolecular Prins-, aza-Prins-, and thia-Prins/Friedel-Crafts cyclizations, respectively. Though the Prins cyclization proceeds smoothly under the influence of Sc(OTf)(3), high conversions and enhanced reaction rates are achieved using a mixture of Sc(OTf)(3) and TsOH (1:3). 相似文献
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V. S. Borkar 《Journal of Optimization Theory and Applications》1995,86(1):251-261
For the ergodic control problem with degenerate diffusions, the existence of an optimal solution is established for various interesting classes of solutions.This research was supported by Grant No. 26/01/92-G from the Department of Atomic Energy, Government of India, Delhi, India. 相似文献
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Vivek S. Borkar 《Annals of Operations Research》1991,29(1):429-438
A new state variable is introduced for the problem of controlling a Markov chain under partial observations, which, under a suitably altered probability measure, has a simple evolution. 相似文献
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A new approach based on occupation measures is introduced for studying stochastic differential games. For two-person zero-sum games, the existence of values and optimal strategies for both players is established for various payoff criteria. ForN-person games, the existence of equilibria in Markov strategies is established for various cases. 相似文献