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2015 ; 11
(2
): 265-73
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Data Mining FAERS to Analyze Molecular Targets of Drugs Highly Associated with
Stevens-Johnson Syndrome
#MMPMID25876064
Burkhart KK
; Abernethy D
; Jackson D
J Med Toxicol
2015[Jun]; 11
(2
): 265-73
PMID25876064
show ga
Drug features that are associated with Stevens-Johnson syndrome (SJS) have not
been fully characterized. A molecular target analysis of the drugs associated
with SJS in the FDA Adverse Event Reporting System (FAERS) may contribute to
mechanistic insights into SJS pathophysiology. The publicly available version of
FAERS was analyzed to identify disproportionality among the molecular targets,
metabolizing enzymes, and transporters for drugs associated with SJS. The FAERS
in-house version was also analyzed for an internal comparison of the drugs most
highly associated with SJS. Cyclooxygenases 1 and 2, carbonic anhydrase 2, and
sodium channel 2 alpha were identified as disproportionately associated with SJS.
Cytochrome P450 (CYPs) 3A4 and 2C9 are disproportionately represented as
metabolizing enzymes of the drugs associated with SJS adverse event reports.
Multidrug resistance protein 1 (MRP-1), organic anion transporter 1 (OAT1), and
PEPT2 were also identified and are highly associated with the transport of these
drugs. A detailed review of the molecular targets identifies important roles for
these targets in immune response. The association with CYP metabolizing enzymes
suggests that reactive metabolites and oxidative stress may have a contributory
role. Drug transporters may enhance intracellular tissue concentrations and also
have vital physiologic roles that impact keratinocyte proliferation and survival.
Data mining FAERS may be used to hypothesize mechanisms for adverse drug events
by identifying molecular targets that are highly associated with drug-induced
adverse events. The information gained may contribute to systems biology disease
models.