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ADME-Enabling Technologies in Drug Design and Development by Donglu Zhang, Sekhar Surapaneni PDF

By Donglu Zhang, Sekhar Surapaneni

ISBN-10: 0470542780

ISBN-13: 9780470542781

A accomplished advisor to state of the art instruments in ADME research

The final decade has noticeable great growth within the improvement of analytical suggestions akin to mass spectrometry and molecular biology instruments, leading to vital advances in drug discovery, rather within the region of absorption, distribution, metabolism, and excretion (ADME).

ADME-Enabling applied sciences in Drug layout and improvement makes a speciality of the present cutting-edge within the box, providing a complete evaluate of the most recent instruments for producing ADME facts in drug discovery. It examines the broadest attainable diversity of obtainable applied sciences, giving readers the knowledge they should pick out the precise software for a given program, a key considered necessary for acquiring favorable ends up in a well timed style for regulatory filings. With over thirty contributed chapters by means of a global crew of specialists, the e-book provides:

  • A thorough exam of present instruments, masking either electronic/mechanical applied sciences and biologically dependent ones

  • Coverage of functions for every know-how, together with key parameters, optimum stipulations for meant effects, protocols, and case studies

  • Detailed dialogue of rising instruments and methods, from stem cells and genetically changed animal types to imaging technologies

  • Numerous figures and diagrams during the text

Scientists and researchers in drug metabolism, pharmacology, medicinal chemistry, pharmaceutics, toxicology, and bioanalytical technological know-how will locate ADME-Enabling applied sciences in Drug layout and improvement a useful advisor to the full drug improvement technique, from discovery to regulatory concerns

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Additional resources for ADME-Enabling Technologies in Drug Design and Development

Example text

However, despite the cost and time involved in synthesizing, purifying, and characterizing compounds, an ADME optimization process with only virtual models are no substitution for the utilization of relevant in vitro and in vivo assays in making key decisions for selecting development candidates. The ideal ADME properties that one should look for in a development candidate are (1) good oral bioavailability, (2) low to moderate blood clearance, (3) ideal volume of distribution (beyond plasma volume), (4) low potential for DDI, (5) low metabolism-dependent toxicity relevant to humans, and (6) a desirable projected human half-life that enables dosing regimen consistent with patient compliance.

Irrespective of test system used, the experimentation should include known substrates and inhibitors to demonstrate the suitability of test systems. Bidirectional transport measurements are preferred and net flux should be calculated for interpretation of results. If the compound has a net flux ratio of >2, then it is considered a substrate and further evaluation should be carried out. If the test compound has an efflux ratio <2, then it is not a Pgp substrate; and follow-up interaction studies are not needed.

Lin JH (2006) CYP induction-mediated drug interactions: In vitro assessment and clinical implications. Pharm Res 23(6):1089–1116. 27. Chu V, Einolf HJ, Evers R, Kumar G, Moore D, Ripp S, Silva J, Sinha V, Sinz M, Skerjanec A (2009) In vitro and in vivo induction of cytochrome p450: A survey of the current practices and recommendations: A pharmaceutical research and manufacturers of America perspective. Drug Metab Dispos 37(7):1339–1354. 28. Xia CQ, Milton MN, Gan LS (2007) Evaluation of drugtransporter interactions using in vitro and in vivo models.

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ADME-Enabling Technologies in Drug Design and Development by Donglu Zhang, Sekhar Surapaneni


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