Reporting Avenues for Concerns Related to Integrity or Fairness

The Drug and Biologic Disposition and Toxicity (DBDT) study section reviews applications related to the disposition and safety of therapeutic agents including small molecule drugs and pro-drugs, biological products such as therapeutic proteins and gene therapies, and phytochemicals/botanicals. The panel reviews studies on how the body’s transporter, enzymatic and other biological processes affect the pharmacokinetic properties and toxicological profiles of drugs and therapeutic biologics. Additionally, this panel reviews applications focused on the development of in vitro, in vivo, and mathematical models for use in understanding and predicting therapeutic agent disposition and safety. Further, studies of how formulation can alter safety and efficacy are within the scope of this panel. It also examines mechanisms of therapeutic agent-induced toxicity as well as how pharmacogenetics and biological processes may impact the action and/or pharmacokinetics of drugs and biologics. Applications reviewed by this panel may have a focus on any cell type, tissue, organ, organ system, or anatomical compartment.

Review Dates

Topics


  • Mechanistic, preclinical, and clinical studies related to the disposition and safety of therapeutic agents (drugs and biologics) including processes of absorption, biotransformation, distribution, excretion and toxicity.
  • Studies investigating mechanisms of nanoparticle toxicity and/or immunogenicity, as well as mechanisms of action of xenobiotics, non-nutrient chemicals and nutrients, including pharmacological effects across multiple organ systems.
  • Toxicity and off target effects of gene therapies.
  • Optimization of lead compounds for absorption, biotransformation, distribution, excretion, and toxicity. Studies may include structure-function relationships for enzymes/transporters/receptors involved in nutrient, non-nutrient chemicals and/or xenobiotic disposition and their toxic effects.
  • Impact of genetics on disposition including pharmacogenetics/pharmacogenomics and toxicogenetics/toxicogenomics.
  • Theoretical, mechanistic, and/or physiologically based modeling of pharmacokinetics, pharmacodynamics, toxicokinetics and toxicodynamics including the development of in vitro and in vivo model systems to study drug and/or biologic disposition and safety.
  • Interactions between therapeutic agents that impact disposition, toxicity, and efficacy such as interactions among xenobiotics (e.g., drug-drug interactions, nutrient-drug interactions, alcohol-drug interactions) involving disposition and response processes.
  • Environmental factors and agents that impact drug and/or biologic disposition including bioavailability, metabolism, pharmacokinetics, and toxicokinetics, including the effect of the microbiome on bioavailability, metabolism and pharmacokinetics of drugs and xenobiotics.
  • Studies of the influence of formulation on disposition, safety, and efficacy.

Shared Interests and Overlaps

There are shared interests in the pharmacology, metabolism and disposition of xenobiotics with Environmental Determinants of Disease (EDD). Applications that emphasize disposition or metabolism and pharmacology of xenobiotics and supraphysiologic levels of nutrient and non-nutrient chemicals (not environmental toxicants) are reviewed in DBDT. Applications that involve environmental toxicants/toxins are reviewed in EDD.

There are shared interests in studies of drug or biologic bioavailability, biotransformation, and/or toxicity with Advancing Therapeutics A (ATA) and MCST (81). Applications that primarily focused on those areas are reviewed in DBDT. Applications that emphasize pilot studies of drug or biologic bioavailability, biotransformation, and/or toxicity as part of the larger proposal are reviewed in ATA or MCST (81).

There are shared interests in involving agents for therapeutic delivery with Drug and Biologic Therapeutic Delivery (DBTD). Applications that focus on the disposition and safety of delivery agents are reviewed in DBDT. Applications that involve fundamental aspects of therapeutic delivery, including controlled or triggered release, intraorgan/intracellular delivery, delivery vehicle development, or targeting strategies are reviewed in DBTD.

There are shared interests in nanosystem/nanotechnology development with Innovations in Nanosystems and Nanotechnology (INN). Applications that emphasize the disposition, safety and toxicity of delivery agents are reviewed in DBDT.  Applications that focus on novel nanotechnology development are reviewed in INN.

There are shared interests in therapeutic systems for nucleic acid delivery with BBBT (81). Applications that emphasize the disposition, safety and toxicity of delivery agents are reviewed in DBDT. Applications that focus on fundamental aspects of nucleic acid delivery are reviewed in BBBT (81).

There are shared interests in the effects of nutrients on the disposition of drugs and xenobiotics with Nutrition and Metabolism in Health and Disease (NMHD). Applications that investigate the disposition of supraphysiologic levels of nutrients are reviewed in DBDT. Applications that emphasize the integrated effects of nutrients on physiological functions and their influence on disease are reviewed in NMHD.

There are shared interests in drug development with Chemical Biology and Probes (CBP). Applications that focus on ADME/tox studies of candidate compounds already synthesized are reviewed in DBDT. Applications that focus on the early-stage development and characterization of novel compounds are reviewed in CBP.

There are shared interests in hepatobiliary transport, liver injury and alcohol liver disease with Hepatobiliary Pathophysiology (HBPP). Applications that investigate alcohol-drug interactions and the contributions of alcohol to pharmacological-induced injury in the liver are reviewed in DBDT. Applications that focus on the pathogenesis of alcoholic liver injury and other liver diseases are reviewed in HBPP.