| dc.description.abstract | The GSRS database was developed by the Global Ingredient Archival System (GINAS) initiative and
contains the molecular structure, classification information and metabolites of compounds used in
human and animal medicinal, food, tobacco, and cosmetic products. Using GSRS, five sub-studies
were performed each investigating a pre-selected SA-ADR relationship. For four sub-studies, the SAADR relationship was described in former studies. For the fifth sub-study, a newly discovered
potential SA-ADR relationship was investigated. For each study, a GSRS search was performed, and it
was extracted if a specific drug-ADR combination was reported disproportionally in VigiLyze, the
global database for Individual Case Safety Reports of the WHO, and in addition the summary of
product characteristics (SmPC) was checked.
First it was shown that the GSRS database could indeed be queried to find relevant structures
containing a number of pre-selected SAs. It was also shown that, based on a specific RM, GSRS
contained sufficient information to highlight drugs that formed similar RMs or contained parts of the
RM in their original structure. Thirdly, the possibilities of searching for drugs containing structural
varieties within one drug class were investigated and this showed the mediating effects of a
substituent on the occurrence of ADRs. This analysis showed the potential usability of the GSRS for
future PV research.
Additionally, it was demonstrated that GSRS could be used to find drugs with diverse therapeutic
indications containing a pre-selected SA. Looking at the SmPCs and reporting rate for the results,
2
signs of the involvement of this SA in the development of Steven-Johnson syndrome and
methemoglobinemia were displayed.
Finally, a possible relationship between a SA that was discovered by looking at the reason behind the
retraction of two fluoroquinolones and the ADR QT prolongation was described. The drugs
containing the SA showed, with one exception, a high reporting rate for QT prolongation, whereas
drugs that did not contain the SA did not.
Implications
This study shows that the GSRS database is a suitable tool for identifying drugs containing a SA. It
can help PV research by finding structurally related drugs in pre- and postmarketing stages. | |
