A new medicinal chemistry blog has an interesting post about “idiosyncratic” drug reactions, adverse reactions that occur in a small set of patients. For any number of reasons, trying to get a handle on unpredictable ADRs in small patient subpopulations is critical for the pharmaceutical industry. I am no authority on such ADRs and suggest reading the original post for more information, including references and the authors views.
Currently, idiosyncratic ADRs are not predictable since their mechanisms are not well understood. This is where I believe that translational research is going to play a strong role. Can we identify potential biomarkers (either metabolic markers or genotypes or anything else) that can help identify potential patient subpopulations that might suffer from idiosyncratic ADRs? The guess here is that we can (and a quick glance at the literature suggests that efforts to this effect are currently underway). What I am not sure about is the diversity of these markers. Can we pin these down to a small enough subset that a product along the lines of the Amplichip can be developed?
Given the likely diversity of markers and the limited mechanistic understanding, idiosyncratic ADRs are likely to remain a problem for the foreseeable feature, but hopefully as we gain a better understanding of disease variation between patient subpopulations, we will get a better handle on the risk associated with idiosyncratic effects. There is a good reason that safety biomarkers are high on the list of topics of discussion at most of the conferences I go to these days.
Patients that demonstrate the ADRs should be extremely interesting to the pharma/FDA. Has anyone began to track and resquence relevant segments of these patients genomes, to determine what genetic markers may explain or predict? Or at least biobanking their samples for a suitable day?
Pesky ADRs
A new medicinal chemistry blog has an interesting post about “idiosyncratic” drug reactions, adverse reactions that occur in a small set of patients. For any number of reasons, trying to get a handle on unpredictable ADRs in small patient subpopulations is critical for the pharmaceutical industry. I am no authority on such ADRs and suggest reading the original post for more information, including references and the authors views.
Currently, idiosyncratic ADRs are not predictable since their mechanisms are not well understood. This is where I believe that translational research is going to play a strong role. Can we identify potential biomarkers (either metabolic markers or genotypes or anything else) that can help identify potential patient subpopulations that might suffer from idiosyncratic ADRs? The guess here is that we can (and a quick glance at the literature suggests that efforts to this effect are currently underway). What I am not sure about is the diversity of these markers. Can we pin these down to a small enough subset that a product along the lines of the Amplichip can be developed?
Given the likely diversity of markers and the limited mechanistic understanding, idiosyncratic ADRs are likely to remain a problem for the foreseeable feature, but hopefully as we gain a better understanding of disease variation between patient subpopulations, we will get a better handle on the risk associated with idiosyncratic effects. There is a good reason that safety biomarkers are high on the list of topics of discussion at most of the conferences I go to these days.
Further Reading:
Jack Uetrecht
CDER: Liver Toxicity
Technorati Tags: Adverse Drug Reactions, Toxicity, Healthcare, Drug Development, Biomarkers