Radiation Protection Dosimetry Advance Access originally published online on May 7, 2009
Radiation Protection Dosimetry 2009 134(3-4):184-190; doi:10.1093/rpd/ncp071
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Therapeutic product disposition in at-risk populations
Therapeutic Products Directorate, Health Canada, Ottawa, ON, Canada K1A 0K9
* Corresponding author: brian_foster{at}hc-sc.gc.ca
In an emergency situation, such as a chemical, biological, radionuclide, nuclear or explosion (CBRNE) event, all patient populations are at increased risk of serious adverse events. Therapeutic product (TP) safety and efficacy depend on the disposition of the product through absorption, distribution, metabolism and excretion. The ability of a patient to benefit from or merely tolerate a TP can be modified by many factors, including but not limited to culture, diet, disease, environmental contaminants, genetic predisposition, stress and socioeconomic status and recent life experiences. Metabolism is considered to have the greatest effect on safety and efficacy, as chemicals not metabolised can accumulate to toxic levels. Inter-individual variances in most drug metabolism enzymes may range up to greater than 1000-fold. The fetus, neonates, infants, individuals with hormonal change, infection or prior exposure to licit or illicit products and the elderly are more susceptible to increased risk of serious adverse health effects. The critically ill are the most at risk. The at-risk populations for a serious adverse event are dependent then on the CBRNE event, their physical and cognitive states and the inter-individual intrinsic and extrinsic factors that affect TP disposition.