Adverse drug
reactions (ADRs) are the 4th major cause of death in the United States and
the cost associated with drug-related morbidity and mortality is estimated
to be $136 billion per year. Surprisingly, very little is known on the
effect of type of diabetes (type 1 vs. type 2), presence of obesity,
agents used to treat diabetes and altered inflammatory mediators on the
disposition of commonly used drugs. The long term goal of this project is
to understand the extent of diabetes effect on the biotransformation and
transport mechanisms governing the disposition of pharmacological agents
aiming to devise individualized treatment strategies for these patients.
Using clinical, translational and experimental methods, this project will
aim to characterize the activity of CYP3A enzymes, responsible for
biotransformation of 60% of all xenobiotics, in type 1 and 2 diabetic
patients and to learn whether diabetics respond differently to inducer or
inhibitors of CYP3A. We also aim to understand the association between
intracellularly expressed inflammatory mediators (IL-1beta, IL-6, TNF-alpha
and IFN-gamma) on drug disposition, aiming to identify an appropriate
“blood based biomarker” to estimate the degree of this alteration.
Describing the effects of diabetes on the disposition of the lipid
lowering agent atorvastatin, one of the most frequently used drugs in the
market, is another goal of this research program. We anticipate that this
research will generate a body of data with direct clinical implication to
improve pharmacotherapy in this patient population.
