By Sean Ekins
This booklet covers key rising applied sciences - precise lower than in regards to the subject - in pharmaceutical R & D and the way they've got considerably impacted (or are at the moment impacting) drug discovery. The cross-disciplinary collaborations implicit in integrating those applied sciences with drug discovery operations will gasoline the engine for destiny suggestions. This publication cuts around the a number of parts of drug discovery, each one bankruptcy authored via pioneers in that box, making for a wide entice the chemical and organic scientists and technologists concerned about drug discovery and improvement.
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Extra resources for Drug Efficacy, Safety, and Biologics Discovery: Emerging Technologies and Tools
Sample text
Finally, it is important to reiterate that the drug efficacy consideration alone is not sufficient for a reliable TI prediction. For example, if a drug-induced side effect is directly linked to hyperantagonism of a target enzyme (as is the case for cerivastatin), a slow dissociation rate and long residence time can potentially exacerbate such a side effect (especially upon repeated drug dosing). ” This can explain why drug-induced organ toxicity typically takes repeated dosing and manifests over longer period of time, as intracellular drug concentrations can reach a toxic level.
The remainder of this chapter will discuss emerging technologies that could make this happen, and provide the authors’ perspectives on challenges in the field. 2 GENERAL APPROACHES IN PREDICTING THE THERAPEUTIC INDEX Predicting a therapeutic index is intrinsically a systems pharmacology and systems toxicology challenge. This exercise no longer deals with a single enzyme or receptor, but with a multiple-component system that includes competing endogenous ligands, co-factors, off-targets, multiple cell types, organs, and tissues.
72. Durham JA, Gandolfi AJ, Bentley JB. Hepatotoxicological evaluation of dantrolene sodium. Drug Chem Toxicol 1984;7:23–40. 73. Watkins PB, Dube LM, Walton-Bowen K, Cameron CM, Kasten LE. Clinical pattern of zileuton-associated liver injury: results of a 12-month study in patients with chronic asthma. Drug Saf 2007;30:805–15. 74. Boelsterli UA. Diclofenac-induced liver injury: a paradigm of idiosyncratic drug toxicity. Toxicol Appl Pharmacol 2003;192:307–22. 75. Wilkening S, Stahl F, Bader A. Comparison of primary human hepatocytes and hepatoma cell line Hepg2 with regard to their biotransformation properties.