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About FDA

Laboratory of Clinical Pharmacology Research Programs

U.S. Mail Only:
Life Sciences Building #64
10903 New Hampshire Ave, 
Room 2067
Silver Spring, MD 20993
Courier Delivery Only:
Life Sciences Bldg. #64
Room 2067, HFD-902
10903 New Hampshire Ave.
Silver Spring, MD  20993

Phone:  (301) 796-0121

Fax:  (301) 796-9814

 Human Hepatotoxicity Model In Vitro


Hepatotoxicity is one of the leading serious adverse drug reactions observed in humans. Recent examples producing liver failure or death include: felbamate, troglitazone, and trovafloxacin. Many adverse drug reactions result from covalent binding of reactive metabolites to critical cellular proteins. Human liver tissue models in vitro can provide a tool for identifying reactive metabolites and evaluating their toxic potential. The use of human tissue avoids the interspecies differences in drug metabolism. Freshly isolated or cryopreserved human hepatocytes whose glutathione pools have been enriched with 35S- or 14C-glutathione will be incubated with drugs and radiolabeled thio-conjugates will be identified as potential reactive metabolites. Enzymatic pathways identified will be modulated to increase the production of reactive metabolites and selected biomarkers will be used to examine their toxic effects on hepatocytes in vitro.

Drug Metabolism and Drug-Drug Interactions


  • Develop emerging technology in directions applicable to regulatory decision-making, including pilot studies to demonstrate utility. 
  • Provide an in-house resource for experimental work, as well as consultations on specific issues arising from INDs and NDAs. 
  • Provide an opportunity for FDA reviewers to participate in hands-on projects.


The primary tools are analytical support and access to fresh human tissue, from liver and other organs, plus a bank of frozen human tissue specimens. A range of additional tools, such as recombinant human enzymes and defined chemical inhibitors, are also utilized. Sub-projects range in scope from a few weeks to over a year.

The work on this project is closely tied to the ongoing review of metabolism and drug interaction data, and was instrumental in developing CDER's Guidance  on this topic.

 PET Probes as Biomarkers for Efficacy


  • Develop the principles which describe optimal positron-labeled probes. 
    • These probes can be used to determine drug distribution in the body, as well as to assess drug impact directly at the target, e.g., receptors, enzymes, or transporters. Overall, the goal is to provide biomarkers for efficacy determination.


Positron Emission Tomography (PET) is an emerging technology which is increasingly being applied to drug development. FDA/CDER has a long-standing interest in the use of Pharmacokinetic-Pharmacodynamic (PK-PD) principles for regulatory decision-making. PET provides a unique opportunity to examine PK-PD directly at the level of the drug target, rather than indirectly via plasma concentrations and/or downstream indicators of target modulation.

Page Last Updated: 08/30/2016
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