Safety testing of drugs

Recent US FDA guidance on safety testing of drug metabolites [5] highlights the importance of measuring major metabolites in human and toxicological species. This increased scrutiny on the role of metabolites in the evaluation of efficacy and safety will lead to increasing demand for metabolites as analytical standards. 

US Food Drug Adminstration (2008) Guidance for Industry, Safety Testing of Drug Metabolites, http //www.fda. gov/cder/guidance/index.htm (last access October 2008). 

Figure 1.33. A decision tree flow diagram describing some of the studies needed to detennine safety of a human drug metabolite. (Food and Drug Administration (2008). Guidance for Industry Safety Testing of Drug Metabolites.)...

FDA Draft Safety Testing of Drug Metabolites (Guidance for Industry June 2005)... 

FDA. Draft Guideline for industry Safety testing of drug metabolites. US FDA, CDER June 2005. 

Prueksaritanont, T., Lin, J.H., and Baillie, T.A., Complicating factors in safety testing of drug metabolites Kinetic differences between generated and preformed metabolites, Toxicol. Appl. Pharm., 217, 143, 2006. 

FDA. CFR title 21, part 361.1—radioactive drugs for certain research uses 2005a. FDA. Safety testing of drug metabolites (draft) 2005b. 

US Food and Drug Administration, Draft guidance for industry on safety testing of drug metabolites. Available at www.fda.gov/cder/guidance. 

U.S.Food and Dmg Administration Guidance for industry safety testing of drug guidance for industry safety testing of drug metabolites (2008)... 

Screening Strategies Metabolite Profiling/Mass Balance Studies Safety Testing of Drug Metabolites Reaction Phenotyping... 

Metabolite quantitation plays an important role in drug discovery and development as the level of metabolites may potentially impact the efficacy and safety of a drug (Baillie et al., 2002 Leclercq et al., 2009 Smith and Obach, 2006). Even for metabolites with no biological activity at the clinical relevant dose, the amount of a specific metabolite formed often reveals a major metabolic pathway that may allow medicinal chemists to block some labile sites on the molecule or soft spots to metabolically stabilize the compound. The recent U.S. Food and Drug Administration (FDA) guidance on Safety Testing of Drug Metabolites further put forward the requirements for... 

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