We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
The application of discovery toxicology and pathology towards the design of safer pharmaceutical lead candidates.
- Authors
Kramer, Jeffrey A.; Sagartz, John E.; Morris, Dale L.
- Abstract
Toxicity is a leading cause of attrition at all stages of the drug development process. The majority of safety-related attrition occurs preclinically, suggesting that approaches to identify 'predictable' preclinical safety liabilities earlier in the drug development process could lead to the design and/or selection of better drug candidates that have increased probabilities of becoming marketed drugs. In this Review, we discuss how the early application of preclinical safety assessment — both new molecular technologies as well as more established approaches such as standard repeat-dose rodent toxicology studies — can identify predictable safety issues earlier in the testing paradigm. The earlier identification of dose-limiting toxicities will provide chemists and toxicologists the opportunity to characterize the dose-limiting toxicities, determine structure–toxicity relationships and minimize or circumvent adverse safety liabilities.
- Subjects
TOXICOLOGY; DRUG development; DRUGS; TOXICITY testing; PHARMACEUTICAL industry; PHARMACOKINETICS; ANTINEOPLASTIC agents; PREVENTIVE medicine
- Publication
Nature Reviews Drug Discovery, 2007, Vol 6, Issue 8, p636
- ISSN
1474-1776
- Publication type
Article
- DOI
10.1038/nrd2378