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Factsheet mb v8b.ai

TRANSILXL
Microsomal Binding Kit

FEATURES AND BENEFITS
 Fast, requires only 20 minutes total assay time  Measures the affinity to human microsomal membranes and  Ready-to-use format in 96-well plate format generating highly  Rapid compound quantification due to immoblized brain membranes with a single lipid bilayer reconstituted from synthe-  Kit includes a spreadsheet for calculation of final results and traffic light natural composition of human liver micromes. TECHNICAL DESCRIPTION
The TRANSILXL Microsomal Binding kit measures the affinity of drugs to human microsomal membranes and determines microsomal binding in stability incubation experiments. This allows the accurate estimation of intrinsic clearance from stability incubations by correcting the experimental clearance with the fraction of drug The kit consists of ready-to-use 96-well microtiter plates. One plate can be used for measuring microsomal binding of up to 12 compounds. The assay requires only 5 steps: (i) addition of drug candidate, (ii) mixing and incubation for 12 minutes, (iii) removal of beads by centrifugation, (iv) sampling of supernatant, and (v) quanti- CAPABILITIES
  Affinity affinity to human liver microsomes   coming soon: fu(mic) for other species Sovicell
Deutscher Platz 5b 04103 Leipzig t. +49 341 520 44 0 f. +49 341 520 44 12 e. info@sovicell.com www.sovicell.com
Application and Relevance
Only free unbound compound is available to be metabolised by the enzymes present in microsomal incubations. Therefore, it is important to consider the extent of binding when performing microsomal clearance studies. Estimated incrinsic clearance rates can be substantially underestimated without correction for microsomal binding (fig. 2). Moreover, it has been shown that the prediction of in vivo compound stability improves substantially when correcting the metabolic rates obtained Microsomal binding not only reduces the concentration of free drug available to be metabolised by CYP enzymes, it also reduces the concentration which is available to inhibit the enzymes. It has been demonstrated that non-specific microsomal binding can account for underestimation of inhibitor potency (i.e., overestimation of IC or K values) when dealing with lipophilic basic drugs. This in turn can lead to an underestimation of risk of drug-drug interactions. In particular, mechanism based inhibitor studies can be affected to a large extent by microsomal binding, because of the high microsome concentrations that are typically employed in these experiments. Hence, the fraction of drug bound to microsomes is also an important correction of experiments assessing the inhibition potential. Intrinsic Clearance
Validation
The intrinsic clearance rate (CL ) is calculated from the A test set of 24 compounds was chosen for validation. observed clearance rate in the microsomal incubation Microsomal binding was measured using the TRANSILXL Microsomal Binding kit and conventional dialysis with microsomes (fig. 3). Both methods yield comparable results which correlate strongly (r2=0.93). Illustration of the influence of microsomal binding Comparison of microsomal binding measurements on clearance rate estimation. Both lines represent using the TRANSIL Microsomal Binding Kit and compounds with identical clearance rate. However, conventional dialysis. The test set comprised alpreno- the compound represented by the dark blue line lol, amantadin, buspirone, carbamazepine, cycloben- does not bind to microsomes, while the compound zaprine, desipramine, diphenhydramine, Enalaprilat, represented by the light blue line binds strongly fexofenadine, fluoxetine, fluvoxamine, faloperidol, f (mic)=10%. Hence, the intrinisc clearance rate of ketoconazol, labetalol, levofloxazine, nalidixic acid, the compound binding to microsomes is highly nortriptyline, promazine, propranolol, sulfasalazine, terazosin, venlafaxine, and warfarin.
PRODUCT INFORMATION
Order Number
TMP-0120-2096 TRANSILXL Microsomal Binding kit Sovicell
Deutscher Platz 5b 04103 Leipzig t. +49 341 520 44 0 f. +49 341 520 44 12 e. info@sovicell.com www.sovicell.com

Source: http://www.sovicell.de/factsheets/FactSheet%20TRANSIL_XL_MB%20V8b.pdf

Microsoft word - hydroxychloroquine_and_ocular_toxicity_final oct 2009.doc

The Royal College of Ophthalmologists Hydroxychloroquine and Ocular Toxicity Recommendations on Screening October 2009 ©  The Royal College of Ophthalmologists 2009 All rights reserved For permission to reproduce any of the content contained herein please contact events@rcophth.ac.uk The Royal College of Ophthalmologists - Hydroxychloroquine and Ocular Toxicity

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