Practical aspects of assessing toxicokinetics and toxicodynamics.
Designing and validating innovative high-throughput screening programs for toxicology requires an in-depth knowledge base on toxicokinetics and toxicodynamics (TK/TD), the two key elements of dose-response. This information is usually obtained from toxicology studies and mechanistically applied in the selection process for new drugs. Validating new toxicological endpoints and applying TK/TD modeling should enhance the predictability of such programs. This review looks at optimal approaches for collecting data and the four components of the TK/TD knowledge base; target specific exposure, toxicodynamics markers - with a focus on kidney, histomorphological correlates in target tissues, and human adverse event information. It is clear that new TK/TD approaches must be developed to create rational screening programs for the future.
Johnson
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Chiron Corporation, Emeryville, CA 94608-2916, USA. dale_johnson@cc.chiron.com
Braeckman
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Wolfgang
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